{"id":298,"date":"2016-08-19T15:35:04","date_gmt":"2016-08-19T15:35:04","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/?post_type=chapter&#038;p=298"},"modified":"2016-08-19T15:35:04","modified_gmt":"2016-08-19T15:35:04","slug":"communication-between-neurons","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/chapter\/communication-between-neurons\/","title":{"raw":"Communication Between Neurons","rendered":"Communication Between Neurons"},"content":{"raw":"<div>\n<div class=\"bcc-box bcc-highlight\">\n<h3>Learning Objectives<\/h3>\n<div>\n<div>\n<ul><li>Explain the differences between the types of graded potentials<\/li>\n\t<li>Categorize the major neurotransmitters by chemical type and effect<\/li>\n<\/ul><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div>\n<ul><li><a href=\"#m46503-fs-id1953788\">Graded Potentials<\/a>\n<ul><li><a href=\"#m46503-fs-id1862445\">Types of Graded Potentials<\/a><\/li>\n\t<li><a href=\"#m46503-fs-id1999161\">Summation<\/a><\/li>\n<\/ul><\/li>\n\t<li><a href=\"#m46503-fs-id2056386\">Synapses<\/a>\n<ul><li><a href=\"#m46503-fs-id1272286\">Neurotransmitter Release<\/a><\/li>\n\t<li><a href=\"#m46503-fs-id1859928\">Neurotransmitter Systems<\/a><\/li>\n<\/ul><\/li>\n<\/ul><\/div>\nThe electrical changes taking place within a neuron, as described in the previous section, are similar to a light switch being turned on. A stimulus starts the depolarization, but the action potential runs on its own once a threshold has been reached. The question is now, \u201cWhat flips the light switch on?\u201d Temporary changes to the cell membrane voltage can result from neurons receiving information from the environment, or from the action of one neuron on another. These special types of potentials influence a neuron and determine whether an action potential will occur or not. Many of these transient signals originate at the synapse.\n<div title=\"Graded Potentials\">\n<div>\n<h3 id=\"m46503-fs-id1953788\">Graded Potentials<\/h3>\n<\/div>\nLocal changes in the membrane potential are called graded potentials and are usually associated with the dendrites of a neuron. The amount of change in the membrane potential is determined by the size of the stimulus that causes it. In the example of testing the temperature of the shower, slightly warm water would only initiate a small change in a thermoreceptor, whereas hot water would cause a large amount of change in the membrane potential.\n\nGraded potentials can be of two sorts, either they are depolarizing or hyperpolarizing (<a title=\"Figure&#xA0;12.25.&#xA0;Graded Potentials\" href=\"#m46503-fig-ch12_05_01\">Figure\u00a012.25<\/a>). For a membrane at the resting potential, a graded potential represents a change in that voltage either above -70 mV or below -70 mV. Depolarizing graded potentials are often the result of Na<sup>+<\/sup>\u00a0or Ca<sup>2+<\/sup>\u00a0entering the cell. Both of these ions have higher concentrations outside the cell than inside; because they have a positive charge, they will move into the cell causing it to become less negative relative to the outside. Hyperpolarizing graded potentials can be caused by K<sup>+<\/sup>\u00a0leaving the cell or Cl<sup>-<\/sup>\u00a0entering the cell. If a positive charge moves out of a cell, the cell becomes more negative; if a negative charge enters the cell, the same thing happens.\n<div id=\"m46503-fig-ch12_05_01\" title=\"Figure&#xA0;12.25.&#xA0;Graded Potentials\">\n<div>\n<div><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152200\/1223_Graded_Potentials-02.jpg\" alt=\"The graph has membrane potential, in millivolts, on the X axis, ranging from negative 90 to positive 30. Time is on the X axis. The left half of the plot line is labeled the depolarizing graded potential. The plot has four progressively larger peaks, with each starting at the resting membrane potential of negative 70. The lowest peak reaches to about negative 65 and is narrow in width, as this represents a small stimulus that causes a small depolarization of the cell membrane. The second peak reaches to about negative 60 but is still narrow. This represents a larger stimulus causing more depolarization. The third peak also reaches to negative 60, but is about twice as wide as the other two peaks. This represents a stimulus of longer duration, which causes a longer lasting depolarization. However, this stimulus is not greater in strength than the previous stimulus. The rightmost peak among the depolarizing graded potentials reaches above the threshold line to about negative 51. This represents a stimulus of sufficient strength to trigger an action potential. The right half of the plot is labeled the hyperpolarizing graded potential. The plot line in this half begins at the resting potential of negative 70, but then drops to more negative membrane potentials. The first peak drops to negative 75 EV, the second peak drops to negative 80 EV and the third peak drops to negative 88 EV. These peaks represent a stimulus that results in hyperpolarization, which is triggered by the activation of specific ion channels in the cell membrane.\" width=\"500\"\/><\/div>\n<\/div>\n<address><strong>Figure\u00a012.25.\u00a0Graded Potentials<\/strong><\/address><address>Graded potentials are temporary changes in the membrane voltage, the characteristics of which depend on the size of the stimulus. Some types of stimuli cause depolarization of the membrane, whereas others cause hyperpolarization. It depends on the specific ion channels that are activated in the cell membrane.<\/address><address>\u00a0<\/address><\/div>\n<div title=\"Types of Graded Potentials\">\n<div>\n<h4 id=\"m46503-fs-id1862445\">Types of Graded Potentials<\/h4>\n<\/div>\nFor the unipolar cells of sensory neurons\u2014both those with free nerve endings and those within encapsulations\u2014graded potentials develop in the dendrites that influence the generation of an action potential in the axon of the same cell. This is called a\u00a0<strong><em>generator potential<\/em><\/strong><a id=\"id733059\"\/>. For other sensory receptor cells, such as taste cells or photoreceptors of the retina, graded potentials in their membranes result in the release of neurotransmitters at synapses with sensory neurons. This is called a\u00a0<strong><em>receptor potential<\/em><\/strong><a id=\"id733074\"\/>.\n\nA\u00a0<strong><em>postsynaptic potential (PSP)<\/em><\/strong><a id=\"id733093\"\/>\u00a0is the graded potential in the dendrites of a neuron that is receiving synapses from other cells. Postsynaptic potentials can be depolarizing or hyperpolarizing. Depolarization in a postsynaptic potential is called an\u00a0<strong><em>excitatory postsynaptic potential (EPSP)<\/em><\/strong><a id=\"id733109\"\/>\u00a0because it causes the membrane potential to move toward threshold. Hyperpolarization in a postsynaptic potential is an\u00a0<strong><em>inhibitory postsynaptic potential (IPSP)<\/em><\/strong><a id=\"id733124\"\/>\u00a0because it causes the membrane potential to move away from threshold.\n\n<\/div>\n<div title=\"Summation\">\n<div>\n<h4 id=\"m46503-fs-id1999161\">Summation<\/h4>\n<\/div>\nAll types of graded potentials will result in small changes of either depolarization or hyperpolarization in the voltage of a membrane. These changes can lead to the neuron reaching threshold if the changes add together, or\u00a0<strong><em>summate<\/em><\/strong><a id=\"id733157\"\/>. The combined effects of different types of graded potentials are illustrated in\u00a0<a title=\"Figure&#xA0;12.26.&#xA0;Postsynaptic Potential Summation\" href=\"#m46503-fig-ch12_05_02\">Figure\u00a012.26<\/a>. If the total change in voltage in the membrane is a positive 15 mV, meaning that the membrane depolarizes from -70 mV to -55 mV, then the graded potentials will result in the membrane reaching threshold.\n\nFor receptor potentials, threshold is not a factor because the change in membrane potential for receptor cells directly causes neurotransmitter release. However, generator potentials can initiate action potentials in the sensory neuron axon, and postsynaptic potentials can initiate an action potential in the axon of other neurons. Graded potentials summate at a specific location at the beginning of the axon to initiate the action potential, namely the initial segment. For sensory neurons, which do not have a cell body between the dendrites and the axon, the initial segment is directly adjacent to the dendritic endings. For all other neurons, the axon hillock is essentially the initial segment of the axon, and it is where summation takes place. These locations have a high density of voltage-gated Na<sup>+<\/sup>\u00a0channels that initiate the depolarizing phase of the action potential.\n\nSummation can be spatial or temporal, meaning it can be the result of multiple graded potentials at different locations on the neuron, or all at the same place but separated in time.\u00a0<strong><em>Spatial summation<\/em><\/strong><a id=\"id733207\"\/>\u00a0is related to associating the activity of multiple inputs to a neuron with each other.\u00a0<strong><em>Temporal summation<\/em><\/strong><a id=\"id733222\"\/>\u00a0is the relationship of multiple action potentials from a single cell resulting in a significant change in the membrane potential. Spatial and temporal summation can act together, as well.\n<div id=\"m46503-fig-ch12_05_02\" title=\"Figure&#xA0;12.26.&#xA0;Postsynaptic Potential Summation\">\n<div>\n<div><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152203\/1224_Post_Synaptic_Potential_Summation.jpg\" alt=\"This graph has membrane potential, in millivolts, on the X axis, ranging from negative 90 to negative 40. Time is on the X axis. The plot line is moving up and down between the resting membrane potential of minus 70 EV and the threshold potential of minus 55 EV. An EPSP causes the plot line to move higher, closer to the threshold potential. An IPSP causes the plot line to move lower, further away from the threshold potential. Toward the right side of the graph, the neuron receives an EPSP that pushes the membrane potential above the threshold, triggering an action potential that causes the plot line to quickly rise above positive 30 EV. The plot line then quickly drops back below minus 70 EV but then gradually increases back to minus 70. A picture of a neuron indicates that excitatory post synaptic potentials are commonly provided by synapses on the neuron&#x2019;s dendrites. Inhibitory post synaptic potentials are commonly provided by synapses near the neuron&#x2019;s axon hillock.\" width=\"380\"\/><\/div>\n<\/div>\n<address><strong>Figure\u00a012.26.\u00a0Postsynaptic Potential Summation<\/strong><\/address><address>The result of summation of postsynaptic potentials is the overall change in the membrane potential. At point A, several different excitatory postsynaptic potentials add up to a large depolarization. At point B, a mix of excitatory and inhibitory postsynaptic potentials result in a different end result for the membrane potential.<\/address><address>\u00a0<\/address><\/div>\n<div id=\"m46503-fs-id1299380\">\n<div\/>\n<div>\n<div class=\"bcc-box bcc-info\">\n<h3>Interactive Link<\/h3>\nWatch this\u00a0<a href=\"http:\/\/openstaxcollege.org\/l\/summation\" target=\"_blank\">video<\/a>\u00a0to learn about summation. The process of converting electrical signals to chemical signals and back requires subtle changes that can result in transient increases or decreases in membrane voltage. To cause a lasting change in the target cell, multiple signals are usually added together, or summated. Does spatial summation have to happen all at once, or can the separate signals arrive on the postsynaptic neuron at slightly different times? Explain your answer.\n\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div title=\"Synapses\">\n<div>\n<h3 id=\"m46503-fs-id2056386\">Synapses<\/h3>\n<\/div>\nThere are two types of connections between electrically active cells, chemical synapses and electrical synapses. In a\u00a0<strong><em>chemical synapse<\/em><\/strong><a id=\"id733355\"\/>, a chemical signal\u2014namely, a neurotransmitter\u2014is released from one cell and it affects the other cell. In an\u00a0<strong><em>electrical synapse<\/em><\/strong><a id=\"id733370\"\/>, there is a direct connection between the two cells so that ions can pass directly from one cell to the next. If one cell is depolarized in an electrical synapse, the joined cell also depolarizes because the ions pass between the cells. Chemical synapses involve the transmission of chemical information from one cell to the next. This section will concentrate on the chemical type of synapse.\n\nAn example of a chemical synapse is the neuromuscular junction (NMJ) described in the chapter on muscle tissue. In the nervous system, there are many more synapses that are essentially the same as the NMJ. All synapses have common characteristics, which can be summarized in this list:\n<div>\n<ul><li>presynaptic element<\/li>\n\t<li>neurotransmitter (packaged in vesicles)<\/li>\n\t<li>synaptic cleft<\/li>\n\t<li>receptor proteins<\/li>\n\t<li>postsynaptic element<\/li>\n\t<li>neurotransmitter elimination or re-uptake<\/li>\n<\/ul><\/div>\nFor the NMJ, these characteristics are as follows: the presynaptic element is the motor neuron's axon terminals, the neurotransmitter is acetylcholine, the synaptic cleft is the space between the cells where the neurotransmitter diffuses, the receptor protein is the nicotinic acetylcholine receptor, the postsynaptic element is the sarcolemma of the muscle cell, and the neurotransmitter is eliminated by acetylcholinesterase. Other synapses are similar to this, and the specifics are different, but they all contain the same characteristics.\n<div title=\"Neurotransmitter Release\">\n<div>\n<h4 id=\"m46503-fs-id1272286\">Neurotransmitter Release<\/h4>\n<\/div>\nWhen an action potential reaches the axon terminals, voltage-gated Ca<sup>2+<\/sup>\u00a0channels in the membrane of the synaptic end bulb open. The concentration of Ca<sup>2+<\/sup>\u00a0increases inside the end bulb, and the Ca<sup>2+<\/sup>\u00a0ion associates with proteins in the outer surface of neurotransmitter vesicles. The Ca<sup>2+<\/sup>\u00a0facilitates the merging of the vesicle with the presynaptic membrane so that the neurotransmitter is released through exocytosis into the small gap between the cells, known as the\u00a0<strong><em>synaptic cleft<\/em><\/strong><a id=\"id733476\"\/>.\n\nOnce in the synaptic cleft, the neurotransmitter diffuses the short distance to the postsynaptic membrane and can interact with neurotransmitter receptors. Receptors are specific for the neurotransmitter, and the two fit together like a key and lock. One neurotransmitter binds to its receptor and will not bind to receptors for other neurotransmitters, making the binding a specific chemical event (<a title=\"Figure&#xA0;12.27.&#xA0;The Synapse\" href=\"#m46503-fig-ch12_05_03\">Figure\u00a012.27<\/a>).\n<div id=\"m46503-fig-ch12_05_03\" title=\"Figure&#xA0;12.27.&#xA0;The Synapse\">\n<div>\n<div><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152206\/1225_Chemical_Synapse.jpg\" alt=\"This diagram shows a postsynaptic neuron. An axon from a presynaptic neuron is synapsing with the dendrites on the post synaptic neuron. The axon of the presynaptic neuron branches into several club shaped axon terminals. A magnified view of one of the synapses reveals that the axon terminal does not contact the dendrite of the postsynaptic neuron. Instead, there is a small space between the two structures, called the synaptic cleft. The axon terminal of the presynaptic neuron contains several synaptic vesicles, each holding about a dozen neurotransmitter particles. The synaptic vesicles travel to the edge of the axon terminal and release their neurotransmitters into the synaptic clefts The neurotransmitters travel through the synaptic cleft and bind to carrier proteins on the postsynaptic neuron that contain receptors foe neurotransmitters.\" width=\"480\"\/><\/div>\n<\/div>\n<address><strong>Figure\u00a012.27.\u00a0The Synapse<\/strong><\/address><address>The synapse is a connection between a neuron and its target cell (which is not necessarily a neuron). The presynaptic element is the synaptic end bulb of the axon where Ca<sup>2+<\/sup>\u00a0enters the bulb to cause vesicle fusion and neurotransmitter release. The neurotransmitter diffuses across the synaptic cleft to bind to its receptor. The neurotransmitter is cleared from the synapse either by enzymatic degradation, neuronal reuptake, or glial reuptake.<\/address><address>\u00a0<\/address><\/div>\n<\/div>\n<div title=\"Neurotransmitter Systems\">\n<div>\n<h4 id=\"m46503-fs-id1859928\">Neurotransmitter Systems<\/h4>\n<\/div>\nThere are several systems of neurotransmitters that are found at various synapses in the nervous system. These groups refer to the chemicals that are the neurotransmitters, and within the groups are specific systems.\n\nThe first group, which is a neurotransmitter system of its own, is the\u00a0<strong><em>cholinergic system<\/em><\/strong><a id=\"id733578\"\/>. It is the system based on acetylcholine. This includes the NMJ as an example of a cholinergic synapse, but cholinergic synapses are found in other parts of the nervous system. They are in the autonomic nervous system, as well as distributed throughout the brain.\n\nThe cholinergic system has two types of receptors, the\u00a0<strong><em>nicotinic receptor<\/em><\/strong><a id=\"id733600\"\/>\u00a0is found in the NMJ as well as other synapses. There is also an acetylcholine receptor known as the<strong>\u00a0<em>muscarinic receptor<\/em><\/strong><a id=\"id733614\"\/>. Both of these receptors are named for drugs that interact with the receptor in addition to acetylcholine. Nicotine will bind to the nicotinic receptor and activate it similar to acetylcholine. Muscarine, a product of certain mushrooms, will bind to the muscarinic receptor. However, nicotine will not bind to the muscarinic receptor and muscarine will not bind to the nicotinic receptor.\n\nAnother group of neurotransmitters are amino acids. This includes glutamate (Glu), GABA (gamma-aminobutyric acid, a derivative of glutamate), and glycine (Gly). These amino acids have an amino group and a carboxyl group in their chemical structures. Glutamate is one of the 20 amino acids that are used to make proteins. Each amino acid neurotransmitter would be part of its own system, namely the glutamatergic, GABAergic, and glycinergic systems. They each have their own receptors and do not interact with each other. Amino acid neurotransmitters are eliminated from the synapse by reuptake. A pump in the cell membrane of the presynaptic element, or sometimes a neighboring glial cell, will clear the amino acid from the synaptic cleft so that it can be recycled, repackaged in vesicles, and released again.\n\nAnother class of neurotransmitter is the\u00a0<strong><em>biogenic amine<\/em><\/strong><a id=\"id733652\"\/>, a group of neurotransmitters that are enzymatically made from amino acids. They have amino groups in them, but no longer have carboxyl groups and are therefore no longer classified as amino acids. Serotonin is made from tryptophan. It is the basis of the serotonergic system, which has its own specific receptors. Serotonin is transported back into the presynaptic cell for repackaging.\n\nOther biogenic amines are made from tyrosine, and include dopamine, norepinephrine, and epinephrine. Dopamine is part of its own system, the dopaminergic system, which has dopamine receptors. Dopamine is removed from the synapse by transport proteins in the presynaptic cell membrane. Norepinephrine and epinephrine belong to the adrenergic neurotransmitter system. The two molecules are very similar and bind to the same receptors, which are referred to as alpha and beta receptors. Norepinephrine and epinephrine are also transported back into the presynaptic cell. The chemical epinephrine (epi- = \u201con\u201d; \u201c-nephrine\u201d = kidney) is also known as adrenaline (renal = \u201ckidney\u201d), and norepinephrine is sometimes referred to as noradrenaline. The adrenal gland produces epinephrine and norepinephrine to be released into the blood stream as hormones.\n\nA\u00a0<strong><em>neuropeptide<\/em><\/strong><a id=\"id733693\"\/>\u00a0is a neurotransmitter molecule made up of chains of amino acids connected by peptide bonds. This is what a protein is, but the term protein implies a certain length to the molecule. Some neuropeptides are quite short, such as met-enkephalin, which is five amino acids long. Others are long, such as beta-endorphin, which is 31 amino acids long. Neuropeptides are often released at synapses in combination with another neurotransmitter, and they often act as hormones in other systems of the body, such as vasoactive intestinal peptide (VIP) or substance P.\n\nThe effect of a neurotransmitter on the postsynaptic element is entirely dependent on the receptor protein. First, if there is no receptor protein in the membrane of the postsynaptic element, then the neurotransmitter has no effect. The depolarizing or hyperpolarizing effect is also dependent on the receptor. When acetylcholine binds to the nicotinic receptor, the postsynaptic cell is depolarized. This is because the receptor is a cation channel and positively charged Na<sup>+<\/sup>\u00a0will rush into the cell. However, when acetylcholine binds to the muscarinic receptor, of which there are several variants, it might cause depolarization or hyperpolarization of the target cell.\n\nThe amino acid neurotransmitters, glutamate, glycine, and GABA, are almost exclusively associated with just one effect. Glutamate is considered an excitatory amino acid, but only because Glu receptors in the adult cause depolarization of the postsynaptic cell. Glycine and GABA are considered inhibitory amino acids, again because their receptors cause hyperpolarization.\n\nThe biogenic amines have mixed effects. For example, the dopamine receptors that are classified as D1 receptors are excitatory whereas D2-type receptors are inhibitory. Biogenic amine receptors and neuropeptide receptors can have even more complex effects because some may not directly affect the membrane potential, but rather have an effect on gene transcription or other metabolic processes in the neuron. The characteristics of the various neurotransmitter systems presented in this section are organized in\u00a0<a title=\"Table&#xA0;12.3.&#xA0;\" href=\"#m46503-tbl-ch12_03\">Table\u00a012.3<\/a>.\n\nThe important thing to remember about neurotransmitters, and signaling chemicals in general, is that the effect is entirely dependent on the receptor. Neurotransmitters bind to one of two classes of receptors at the cell surface, ionotropic or metabotropic (<a title=\"Figure&#xA0;12.28.&#xA0;Receptor Types\" href=\"#m46503-fig-ch12_05_04\">Figure\u00a012.28<\/a>). Ionotropic receptors are ligand-gated ion channels, such as the nicotinic receptor for acetylcholine or the glycine receptor. A\u00a0<strong><em>metabotropic receptor<\/em><\/strong><a id=\"id733776\"\/>\u00a0involves a complex of proteins that result in metabolic changes within the cell. The receptor complex includes the transmembrane receptor protein, a G protein, and an effector protein. The neurotransmitter, referred to as the first messenger, binds to the receptor protein on the extracellular surface of the cell, and the intracellular side of the protein initiates activity of the G protein. The\u00a0<strong><em>G protein<\/em><\/strong><a id=\"id733793\"\/>\u00a0is a guanosine triphosphate (GTP) hydrolase that physically moves from the receptor protein to the effector protein to activate the latter. An\u00a0<strong><em>effector protein<\/em><\/strong><a id=\"id733807\"\/>\u00a0is an enzyme that catalyzes the generation of a new molecule, which acts as the intracellular mediator of the signal that binds to the receptor. This intracellular mediator is called the second messenger.\n\nDifferent receptors use different second messengers. Two common examples of second messengers are cyclic adenosine monophosphate (cAMP) and inositol triphosphate (IP<sub>3<\/sub>). The enzyme adenylate cyclase (an example of an effector protein) makes cAMP, and phospholipase C is the enzyme that makes IP<sub>3<\/sub>. Second messengers, after they are produced by the effector protein, cause metabolic changes within the cell. These changes are most likely the activation of other enzymes in the cell. In neurons, they often modify ion channels, either opening or closing them. These enzymes can also cause changes in the cell, such as the activation of genes in the nucleus, and therefore the increased synthesis of proteins. In neurons, these kinds of changes are often the basis of stronger connections between cells at the synapse and may be the basis of learning and memory.\n<div id=\"m46503-fig-ch12_05_04\" title=\"Figure&#xA0;12.28.&#xA0;Receptor Types\">\n<div>\n<div><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152210\/1226_Receptor_Types.jpg\" alt=\"This diagram contains two images, labeled A and B. Both images show a cross section of a postsynaptic membrane. There are two proteins embedded in each of the two membrane cross sections. In diagram A, direct activation brings about an immediate response. Here, both of the membrane proteins are ion channels. Several hexagonal neurotransmitters bind to ionotropic receptors on the extracellular fluid side of the channels. The binding of neurotransmitters causes the channels to open, allowing ions to flow from the extracellular fluid into the cytosol. Image B shows indirect activation, which involves a prolonged response, amplified over time. Here, one of the cell membrane proteins is solid while the other is a channel. Neurotransmitters bind to metabotropic receptors on the extracellular side of the solid protein. This triggers the solid protein to activate a G protein in the cytoplasm. The G protein binds to an effector protein in the cytoplasm, which results in the production of several second messenger particles. The second messenger activates enzymes that open the channel protein, allowing ions to enter the cytoplasm.\" width=\"450\"\/><\/div>\n<\/div>\n<address><strong>Figure\u00a012.28.\u00a0Receptor Types<\/strong><\/address><address>(a) An ionotropic receptor is a channel that opens when the neurotransmitter binds to it. (b) A metabotropic receptor is a complex that causes metabolic changes in the cell when the neurotransmitter binds to it (1). After binding, the G protein hydrolyzes GTP and moves to the effector protein (2). When the G protein contacts the effector protein, a second messenger is generated, such as cAMP (3). The second messenger can then go on to cause changes in the neuron, such as opening or closing ion channels, metabolic changes, and changes in gene transcription.<\/address><\/div>\n<div id=\"m46503-fs-id1739406\">\n<div\/>\n<div\/>\n<div>\n<div class=\"bcc-box bcc-info\">\n<h3>Interactive Link<\/h3>\nWatch this\u00a0<a href=\"http:\/\/openstaxcollege.org\/l\/neurotrans\" target=\"_blank\">video<\/a>\u00a0to learn about the release of a neurotransmitter. The action potential reaches the end of the axon, called the axon terminal, and a chemical signal is released to tell the target cell to do something\u2014either to initiate a new action potential, or to suppress that activity. In a very short space, the electrical signal of the action potential is changed into the chemical signal of a neurotransmitter and then back to electrical changes in the target cell membrane. What is the importance of voltage-gated calcium channels in the release of neurotransmitters?\n\n<\/div>\n<a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images-archive-read-only\/wp-content\/uploads\/sites\/198\/2014\/11\/20090409\/Screen-Shot-2014-11-13-at-3.17.53-PM.png\"><img class=\"alignnone wp-image-2514 size-full\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152214\/Screen-Shot-2014-11-13-at-3.17.53-PM.png\" alt=\"Screen Shot 2014-11-13 at 3.17.53 PM\" width=\"578\" height=\"362\"\/><\/a>\n\n<\/div>\n<\/div>\n<h2 id=\"m46503-tbl-ch12_03\">Disorders of the Nervous System<\/h2>\n<div id=\"m46503-fs-id722894\">\n<div class=\"bcc-box bcc-success\">\n<div>\n<p title=\"Nervous System\">The underlying cause of some neurodegenerative diseases, such as Alzheimer\u2019s and Parkinson\u2019s, appears to be related to proteins\u2014specifically, to proteins behaving badly. One of the strongest theories of what causes Alzheimer\u2019s disease is based on the accumulation of beta-amyloid plaques, dense conglomerations of a protein that is not functioning correctly. Parkinson\u2019s disease is linked to an increase in a protein known as alpha-synuclein that is toxic to the cells of the substantia nigra nucleus in the midbrain.<\/p>\nFor proteins to function correctly, they are dependent on their three-dimensional shape. The linear sequence of amino acids folds into a three-dimensional shape that is based on the interactions between and among those amino acids. When the folding is disturbed, and proteins take on a different shape, they stop functioning correctly. But the disease is not necessarily the result of functional loss of these proteins; rather, these altered proteins start to accumulate and may become toxic. For example, in Alzheimer\u2019s, the hallmark of the disease is the accumulation of these amyloid plaques in the cerebral cortex. The term coined to describe this sort of disease is \u201cproteopathy\u201d and it includes other diseases. Creutzfeld-Jacob disease, the human variant of the prion disease known as mad cow disease in the bovine, also involves the accumulation of amyloid plaques, similar to Alzheimer\u2019s. Diseases of other organ systems can fall into this group as well, such as cystic fibrosis or type 2 diabetes. Recognizing the relationship between these diseases has suggested new therapeutic possibilities. Interfering with the accumulation of the proteins, and possibly as early as their original production within the cell, may unlock new ways to alleviate these devastating diseases.\n\n<\/div>\n<\/div>\n\u00a0\n\n<\/div>\n<\/div>\n<\/div>","rendered":"<div>\n<div class=\"bcc-box bcc-highlight\">\n<h3>Learning Objectives<\/h3>\n<div>\n<div>\n<ul>\n<li>Explain the differences between the types of graded potentials<\/li>\n<li>Categorize the major neurotransmitters by chemical type and effect<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div>\n<ul>\n<li><a href=\"#m46503-fs-id1953788\">Graded Potentials<\/a>\n<ul>\n<li><a href=\"#m46503-fs-id1862445\">Types of Graded Potentials<\/a><\/li>\n<li><a href=\"#m46503-fs-id1999161\">Summation<\/a><\/li>\n<\/ul>\n<\/li>\n<li><a href=\"#m46503-fs-id2056386\">Synapses<\/a>\n<ul>\n<li><a href=\"#m46503-fs-id1272286\">Neurotransmitter Release<\/a><\/li>\n<li><a href=\"#m46503-fs-id1859928\">Neurotransmitter Systems<\/a><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/div>\n<p>The electrical changes taking place within a neuron, as described in the previous section, are similar to a light switch being turned on. A stimulus starts the depolarization, but the action potential runs on its own once a threshold has been reached. The question is now, \u201cWhat flips the light switch on?\u201d Temporary changes to the cell membrane voltage can result from neurons receiving information from the environment, or from the action of one neuron on another. These special types of potentials influence a neuron and determine whether an action potential will occur or not. Many of these transient signals originate at the synapse.<\/p>\n<div title=\"Graded Potentials\">\n<div>\n<h3 id=\"m46503-fs-id1953788\">Graded Potentials<\/h3>\n<\/div>\n<p>Local changes in the membrane potential are called graded potentials and are usually associated with the dendrites of a neuron. The amount of change in the membrane potential is determined by the size of the stimulus that causes it. In the example of testing the temperature of the shower, slightly warm water would only initiate a small change in a thermoreceptor, whereas hot water would cause a large amount of change in the membrane potential.<\/p>\n<p>Graded potentials can be of two sorts, either they are depolarizing or hyperpolarizing (<a title=\"Figure&#xa0;12.25.&#xa0;Graded Potentials\" href=\"#m46503-fig-ch12_05_01\">Figure\u00a012.25<\/a>). For a membrane at the resting potential, a graded potential represents a change in that voltage either above -70 mV or below -70 mV. Depolarizing graded potentials are often the result of Na<sup>+<\/sup>\u00a0or Ca<sup>2+<\/sup>\u00a0entering the cell. Both of these ions have higher concentrations outside the cell than inside; because they have a positive charge, they will move into the cell causing it to become less negative relative to the outside. Hyperpolarizing graded potentials can be caused by K<sup>+<\/sup>\u00a0leaving the cell or Cl<sup>&#8211;<\/sup>\u00a0entering the cell. If a positive charge moves out of a cell, the cell becomes more negative; if a negative charge enters the cell, the same thing happens.<\/p>\n<div id=\"m46503-fig-ch12_05_01\" title=\"Figure&#xa0;12.25.&#xa0;Graded Potentials\">\n<div>\n<div><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152200\/1223_Graded_Potentials-02.jpg\" alt=\"The graph has membrane potential, in millivolts, on the X axis, ranging from negative 90 to positive 30. Time is on the X axis. The left half of the plot line is labeled the depolarizing graded potential. The plot has four progressively larger peaks, with each starting at the resting membrane potential of negative 70. The lowest peak reaches to about negative 65 and is narrow in width, as this represents a small stimulus that causes a small depolarization of the cell membrane. The second peak reaches to about negative 60 but is still narrow. This represents a larger stimulus causing more depolarization. The third peak also reaches to negative 60, but is about twice as wide as the other two peaks. This represents a stimulus of longer duration, which causes a longer lasting depolarization. However, this stimulus is not greater in strength than the previous stimulus. The rightmost peak among the depolarizing graded potentials reaches above the threshold line to about negative 51. This represents a stimulus of sufficient strength to trigger an action potential. The right half of the plot is labeled the hyperpolarizing graded potential. The plot line in this half begins at the resting potential of negative 70, but then drops to more negative membrane potentials. The first peak drops to negative 75 EV, the second peak drops to negative 80 EV and the third peak drops to negative 88 EV. These peaks represent a stimulus that results in hyperpolarization, which is triggered by the activation of specific ion channels in the cell membrane.\" width=\"500\" \/><\/div>\n<\/div>\n<address><strong>Figure\u00a012.25.\u00a0Graded Potentials<\/strong><\/address>\n<address>Graded potentials are temporary changes in the membrane voltage, the characteristics of which depend on the size of the stimulus. Some types of stimuli cause depolarization of the membrane, whereas others cause hyperpolarization. It depends on the specific ion channels that are activated in the cell membrane.<\/address>\n<address>\u00a0<\/address>\n<\/div>\n<div title=\"Types of Graded Potentials\">\n<div>\n<h4 id=\"m46503-fs-id1862445\">Types of Graded Potentials<\/h4>\n<\/div>\n<p>For the unipolar cells of sensory neurons\u2014both those with free nerve endings and those within encapsulations\u2014graded potentials develop in the dendrites that influence the generation of an action potential in the axon of the same cell. This is called a\u00a0<strong><em>generator potential<\/em><\/strong><a id=\"id733059\">. For other sensory receptor cells, such as taste cells or photoreceptors of the retina, graded potentials in their membranes result in the release of neurotransmitters at synapses with sensory neurons. This is called a\u00a0<strong><em>receptor potential<\/em><\/strong><\/a><a id=\"id733074\">.<\/p>\n<p>A\u00a0<strong><em>postsynaptic potential (PSP)<\/em><\/strong><\/a><a id=\"id733093\">\u00a0is the graded potential in the dendrites of a neuron that is receiving synapses from other cells. Postsynaptic potentials can be depolarizing or hyperpolarizing. Depolarization in a postsynaptic potential is called an\u00a0<strong><em>excitatory postsynaptic potential (EPSP)<\/em><\/strong><\/a><a id=\"id733109\">\u00a0because it causes the membrane potential to move toward threshold. Hyperpolarization in a postsynaptic potential is an\u00a0<strong><em>inhibitory postsynaptic potential (IPSP)<\/em><\/strong><\/a><a id=\"id733124\">\u00a0because it causes the membrane potential to move away from threshold.<\/p>\n<p><\/a><\/div>\n<div title=\"Summation\">\n<div>\n<h4 id=\"m46503-fs-id1999161\">Summation<\/h4>\n<\/div>\n<p>All types of graded potentials will result in small changes of either depolarization or hyperpolarization in the voltage of a membrane. These changes can lead to the neuron reaching threshold if the changes add together, or\u00a0<strong><em>summate<\/em><\/strong><a id=\"id733157\">. The combined effects of different types of graded potentials are illustrated in\u00a0<\/a><a title=\"Figure&#xa0;12.26.&#xa0;Postsynaptic Potential Summation\" href=\"#m46503-fig-ch12_05_02\">Figure\u00a012.26<\/a>. If the total change in voltage in the membrane is a positive 15 mV, meaning that the membrane depolarizes from -70 mV to -55 mV, then the graded potentials will result in the membrane reaching threshold.<\/p>\n<p>For receptor potentials, threshold is not a factor because the change in membrane potential for receptor cells directly causes neurotransmitter release. However, generator potentials can initiate action potentials in the sensory neuron axon, and postsynaptic potentials can initiate an action potential in the axon of other neurons. Graded potentials summate at a specific location at the beginning of the axon to initiate the action potential, namely the initial segment. For sensory neurons, which do not have a cell body between the dendrites and the axon, the initial segment is directly adjacent to the dendritic endings. For all other neurons, the axon hillock is essentially the initial segment of the axon, and it is where summation takes place. These locations have a high density of voltage-gated Na<sup>+<\/sup>\u00a0channels that initiate the depolarizing phase of the action potential.<\/p>\n<p>Summation can be spatial or temporal, meaning it can be the result of multiple graded potentials at different locations on the neuron, or all at the same place but separated in time.\u00a0<strong><em>Spatial summation<\/em><\/strong><a id=\"id733207\">\u00a0is related to associating the activity of multiple inputs to a neuron with each other.\u00a0<strong><em>Temporal summation<\/em><\/strong><\/a><a id=\"id733222\">\u00a0is the relationship of multiple action potentials from a single cell resulting in a significant change in the membrane potential. Spatial and temporal summation can act together, as well.<\/p>\n<div id=\"m46503-fig-ch12_05_02\" title=\"Figure&#xa0;12.26.&#xa0;Postsynaptic Potential Summation\">\n<div>\n<div><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152203\/1224_Post_Synaptic_Potential_Summation.jpg\" alt=\"This graph has membrane potential, in millivolts, on the X axis, ranging from negative 90 to negative 40. Time is on the X axis. The plot line is moving up and down between the resting membrane potential of minus 70 EV and the threshold potential of minus 55 EV. An EPSP causes the plot line to move higher, closer to the threshold potential. An IPSP causes the plot line to move lower, further away from the threshold potential. Toward the right side of the graph, the neuron receives an EPSP that pushes the membrane potential above the threshold, triggering an action potential that causes the plot line to quickly rise above positive 30 EV. The plot line then quickly drops back below minus 70 EV but then gradually increases back to minus 70. A picture of a neuron indicates that excitatory post synaptic potentials are commonly provided by synapses on the neuron&#x2019;s dendrites. Inhibitory post synaptic potentials are commonly provided by synapses near the neuron&#x2019;s axon hillock.\" width=\"380\" \/><\/div>\n<\/div>\n<\/div>\n<p><\/a><\/p>\n<address><strong>Figure\u00a012.26.\u00a0Postsynaptic Potential Summation<\/strong><\/address>\n<address>The result of summation of postsynaptic potentials is the overall change in the membrane potential. At point A, several different excitatory postsynaptic potentials add up to a large depolarization. At point B, a mix of excitatory and inhibitory postsynaptic potentials result in a different end result for the membrane potential.<\/address>\n<address>\u00a0<\/address>\n<\/div>\n<div id=\"m46503-fs-id1299380\">\n<div>\n<div>\n<div class=\"bcc-box bcc-info\">\n<h3>Interactive Link<\/h3>\n<p>Watch this\u00a0<a href=\"http:\/\/openstaxcollege.org\/l\/summation\" target=\"_blank\">video<\/a>\u00a0to learn about summation. The process of converting electrical signals to chemical signals and back requires subtle changes that can result in transient increases or decreases in membrane voltage. To cause a lasting change in the target cell, multiple signals are usually added together, or summated. Does spatial summation have to happen all at once, or can the separate signals arrive on the postsynaptic neuron at slightly different times? Explain your answer.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div title=\"Synapses\">\n<div>\n<h3 id=\"m46503-fs-id2056386\">Synapses<\/h3>\n<\/div>\n<p>There are two types of connections between electrically active cells, chemical synapses and electrical synapses. In a\u00a0<strong><em>chemical synapse<\/em><\/strong><a id=\"id733355\">, a chemical signal\u2014namely, a neurotransmitter\u2014is released from one cell and it affects the other cell. In an\u00a0<strong><em>electrical synapse<\/em><\/strong><\/a><a id=\"id733370\">, there is a direct connection between the two cells so that ions can pass directly from one cell to the next. If one cell is depolarized in an electrical synapse, the joined cell also depolarizes because the ions pass between the cells. Chemical synapses involve the transmission of chemical information from one cell to the next. This section will concentrate on the chemical type of synapse.<\/p>\n<p>An example of a chemical synapse is the neuromuscular junction (NMJ) described in the chapter on muscle tissue. In the nervous system, there are many more synapses that are essentially the same as the NMJ. All synapses have common characteristics, which can be summarized in this list:<\/p>\n<div>\n<ul>\n<li>presynaptic element<\/li>\n<li>neurotransmitter (packaged in vesicles)<\/li>\n<li>synaptic cleft<\/li>\n<li>receptor proteins<\/li>\n<li>postsynaptic element<\/li>\n<li>neurotransmitter elimination or re-uptake<\/li>\n<\/ul>\n<\/div>\n<p>For the NMJ, these characteristics are as follows: the presynaptic element is the motor neuron&#8217;s axon terminals, the neurotransmitter is acetylcholine, the synaptic cleft is the space between the cells where the neurotransmitter diffuses, the receptor protein is the nicotinic acetylcholine receptor, the postsynaptic element is the sarcolemma of the muscle cell, and the neurotransmitter is eliminated by acetylcholinesterase. Other synapses are similar to this, and the specifics are different, but they all contain the same characteristics.<\/p>\n<div title=\"Neurotransmitter Release\">\n<div>\n<h4 id=\"m46503-fs-id1272286\">Neurotransmitter Release<\/h4>\n<\/div>\n<p>When an action potential reaches the axon terminals, voltage-gated Ca<sup>2+<\/sup>\u00a0channels in the membrane of the synaptic end bulb open. The concentration of Ca<sup>2+<\/sup>\u00a0increases inside the end bulb, and the Ca<sup>2+<\/sup>\u00a0ion associates with proteins in the outer surface of neurotransmitter vesicles. The Ca<sup>2+<\/sup>\u00a0facilitates the merging of the vesicle with the presynaptic membrane so that the neurotransmitter is released through exocytosis into the small gap between the cells, known as the\u00a0<strong><em>synaptic cleft<\/em><\/strong><\/div>\n<p><\/a><a id=\"id733476\">.<\/p>\n<p>Once in the synaptic cleft, the neurotransmitter diffuses the short distance to the postsynaptic membrane and can interact with neurotransmitter receptors. Receptors are specific for the neurotransmitter, and the two fit together like a key and lock. One neurotransmitter binds to its receptor and will not bind to receptors for other neurotransmitters, making the binding a specific chemical event (<\/a><a title=\"Figure&#xa0;12.27.&#xa0;The Synapse\" href=\"#m46503-fig-ch12_05_03\">Figure\u00a012.27<\/a>).<\/p>\n<div id=\"m46503-fig-ch12_05_03\" title=\"Figure&#xa0;12.27.&#xa0;The Synapse\">\n<div>\n<div><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152206\/1225_Chemical_Synapse.jpg\" alt=\"This diagram shows a postsynaptic neuron. An axon from a presynaptic neuron is synapsing with the dendrites on the post synaptic neuron. The axon of the presynaptic neuron branches into several club shaped axon terminals. A magnified view of one of the synapses reveals that the axon terminal does not contact the dendrite of the postsynaptic neuron. Instead, there is a small space between the two structures, called the synaptic cleft. The axon terminal of the presynaptic neuron contains several synaptic vesicles, each holding about a dozen neurotransmitter particles. The synaptic vesicles travel to the edge of the axon terminal and release their neurotransmitters into the synaptic clefts The neurotransmitters travel through the synaptic cleft and bind to carrier proteins on the postsynaptic neuron that contain receptors foe neurotransmitters.\" width=\"480\" \/><\/div>\n<\/div>\n<address><strong>Figure\u00a012.27.\u00a0The Synapse<\/strong><\/address>\n<address>The synapse is a connection between a neuron and its target cell (which is not necessarily a neuron). The presynaptic element is the synaptic end bulb of the axon where Ca<sup>2+<\/sup>\u00a0enters the bulb to cause vesicle fusion and neurotransmitter release. The neurotransmitter diffuses across the synaptic cleft to bind to its receptor. The neurotransmitter is cleared from the synapse either by enzymatic degradation, neuronal reuptake, or glial reuptake.<\/address>\n<address>\u00a0<\/address>\n<\/div>\n<\/div>\n<div title=\"Neurotransmitter Systems\">\n<div>\n<h4 id=\"m46503-fs-id1859928\">Neurotransmitter Systems<\/h4>\n<\/div>\n<p>There are several systems of neurotransmitters that are found at various synapses in the nervous system. These groups refer to the chemicals that are the neurotransmitters, and within the groups are specific systems.<\/p>\n<p>The first group, which is a neurotransmitter system of its own, is the\u00a0<strong><em>cholinergic system<\/em><\/strong><a id=\"id733578\">. It is the system based on acetylcholine. This includes the NMJ as an example of a cholinergic synapse, but cholinergic synapses are found in other parts of the nervous system. They are in the autonomic nervous system, as well as distributed throughout the brain.<\/p>\n<p>The cholinergic system has two types of receptors, the\u00a0<strong><em>nicotinic receptor<\/em><\/strong><\/a><a id=\"id733600\">\u00a0is found in the NMJ as well as other synapses. There is also an acetylcholine receptor known as the<strong>\u00a0<em>muscarinic receptor<\/em><\/strong><\/a><a id=\"id733614\">. Both of these receptors are named for drugs that interact with the receptor in addition to acetylcholine. Nicotine will bind to the nicotinic receptor and activate it similar to acetylcholine. Muscarine, a product of certain mushrooms, will bind to the muscarinic receptor. However, nicotine will not bind to the muscarinic receptor and muscarine will not bind to the nicotinic receptor.<\/p>\n<p>Another group of neurotransmitters are amino acids. This includes glutamate (Glu), GABA (gamma-aminobutyric acid, a derivative of glutamate), and glycine (Gly). These amino acids have an amino group and a carboxyl group in their chemical structures. Glutamate is one of the 20 amino acids that are used to make proteins. Each amino acid neurotransmitter would be part of its own system, namely the glutamatergic, GABAergic, and glycinergic systems. They each have their own receptors and do not interact with each other. Amino acid neurotransmitters are eliminated from the synapse by reuptake. A pump in the cell membrane of the presynaptic element, or sometimes a neighboring glial cell, will clear the amino acid from the synaptic cleft so that it can be recycled, repackaged in vesicles, and released again.<\/p>\n<p>Another class of neurotransmitter is the\u00a0<strong><em>biogenic amine<\/em><\/strong><\/a><a id=\"id733652\">, a group of neurotransmitters that are enzymatically made from amino acids. They have amino groups in them, but no longer have carboxyl groups and are therefore no longer classified as amino acids. Serotonin is made from tryptophan. It is the basis of the serotonergic system, which has its own specific receptors. Serotonin is transported back into the presynaptic cell for repackaging.<\/p>\n<p>Other biogenic amines are made from tyrosine, and include dopamine, norepinephrine, and epinephrine. Dopamine is part of its own system, the dopaminergic system, which has dopamine receptors. Dopamine is removed from the synapse by transport proteins in the presynaptic cell membrane. Norepinephrine and epinephrine belong to the adrenergic neurotransmitter system. The two molecules are very similar and bind to the same receptors, which are referred to as alpha and beta receptors. Norepinephrine and epinephrine are also transported back into the presynaptic cell. The chemical epinephrine (epi- = \u201con\u201d; \u201c-nephrine\u201d = kidney) is also known as adrenaline (renal = \u201ckidney\u201d), and norepinephrine is sometimes referred to as noradrenaline. The adrenal gland produces epinephrine and norepinephrine to be released into the blood stream as hormones.<\/p>\n<p>A\u00a0<strong><em>neuropeptide<\/em><\/strong><\/a><a id=\"id733693\">\u00a0is a neurotransmitter molecule made up of chains of amino acids connected by peptide bonds. This is what a protein is, but the term protein implies a certain length to the molecule. Some neuropeptides are quite short, such as met-enkephalin, which is five amino acids long. Others are long, such as beta-endorphin, which is 31 amino acids long. Neuropeptides are often released at synapses in combination with another neurotransmitter, and they often act as hormones in other systems of the body, such as vasoactive intestinal peptide (VIP) or substance P.<\/p>\n<p>The effect of a neurotransmitter on the postsynaptic element is entirely dependent on the receptor protein. First, if there is no receptor protein in the membrane of the postsynaptic element, then the neurotransmitter has no effect. The depolarizing or hyperpolarizing effect is also dependent on the receptor. When acetylcholine binds to the nicotinic receptor, the postsynaptic cell is depolarized. This is because the receptor is a cation channel and positively charged Na<sup>+<\/sup>\u00a0will rush into the cell. However, when acetylcholine binds to the muscarinic receptor, of which there are several variants, it might cause depolarization or hyperpolarization of the target cell.<\/p>\n<p>The amino acid neurotransmitters, glutamate, glycine, and GABA, are almost exclusively associated with just one effect. Glutamate is considered an excitatory amino acid, but only because Glu receptors in the adult cause depolarization of the postsynaptic cell. Glycine and GABA are considered inhibitory amino acids, again because their receptors cause hyperpolarization.<\/p>\n<p>The biogenic amines have mixed effects. For example, the dopamine receptors that are classified as D1 receptors are excitatory whereas D2-type receptors are inhibitory. Biogenic amine receptors and neuropeptide receptors can have even more complex effects because some may not directly affect the membrane potential, but rather have an effect on gene transcription or other metabolic processes in the neuron. The characteristics of the various neurotransmitter systems presented in this section are organized in\u00a0<\/a><a title=\"Table&#xa0;12.3.&#xa0;\" href=\"#m46503-tbl-ch12_03\">Table\u00a012.3<\/a>.<\/p>\n<p>The important thing to remember about neurotransmitters, and signaling chemicals in general, is that the effect is entirely dependent on the receptor. Neurotransmitters bind to one of two classes of receptors at the cell surface, ionotropic or metabotropic (<a title=\"Figure&#xa0;12.28.&#xa0;Receptor Types\" href=\"#m46503-fig-ch12_05_04\">Figure\u00a012.28<\/a>). Ionotropic receptors are ligand-gated ion channels, such as the nicotinic receptor for acetylcholine or the glycine receptor. A\u00a0<strong><em>metabotropic receptor<\/em><\/strong><a id=\"id733776\">\u00a0involves a complex of proteins that result in metabolic changes within the cell. The receptor complex includes the transmembrane receptor protein, a G protein, and an effector protein. The neurotransmitter, referred to as the first messenger, binds to the receptor protein on the extracellular surface of the cell, and the intracellular side of the protein initiates activity of the G protein. The\u00a0<strong><em>G protein<\/em><\/strong><\/a><a id=\"id733793\">\u00a0is a guanosine triphosphate (GTP) hydrolase that physically moves from the receptor protein to the effector protein to activate the latter. An\u00a0<strong><em>effector protein<\/em><\/strong><\/a><a id=\"id733807\">\u00a0is an enzyme that catalyzes the generation of a new molecule, which acts as the intracellular mediator of the signal that binds to the receptor. This intracellular mediator is called the second messenger.<\/p>\n<p>Different receptors use different second messengers. Two common examples of second messengers are cyclic adenosine monophosphate (cAMP) and inositol triphosphate (IP<sub>3<\/sub>). The enzyme adenylate cyclase (an example of an effector protein) makes cAMP, and phospholipase C is the enzyme that makes IP<sub>3<\/sub>. Second messengers, after they are produced by the effector protein, cause metabolic changes within the cell. These changes are most likely the activation of other enzymes in the cell. In neurons, they often modify ion channels, either opening or closing them. These enzymes can also cause changes in the cell, such as the activation of genes in the nucleus, and therefore the increased synthesis of proteins. In neurons, these kinds of changes are often the basis of stronger connections between cells at the synapse and may be the basis of learning and memory.<\/p>\n<div id=\"m46503-fig-ch12_05_04\" title=\"Figure&#xa0;12.28.&#xa0;Receptor Types\">\n<div>\n<div><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152210\/1226_Receptor_Types.jpg\" alt=\"This diagram contains two images, labeled A and B. Both images show a cross section of a postsynaptic membrane. There are two proteins embedded in each of the two membrane cross sections. In diagram A, direct activation brings about an immediate response. Here, both of the membrane proteins are ion channels. Several hexagonal neurotransmitters bind to ionotropic receptors on the extracellular fluid side of the channels. The binding of neurotransmitters causes the channels to open, allowing ions to flow from the extracellular fluid into the cytosol. Image B shows indirect activation, which involves a prolonged response, amplified over time. Here, one of the cell membrane proteins is solid while the other is a channel. Neurotransmitters bind to metabotropic receptors on the extracellular side of the solid protein. This triggers the solid protein to activate a G protein in the cytoplasm. The G protein binds to an effector protein in the cytoplasm, which results in the production of several second messenger particles. The second messenger activates enzymes that open the channel protein, allowing ions to enter the cytoplasm.\" width=\"450\" \/><\/div>\n<\/div>\n<\/div>\n<p><\/a><\/p>\n<address><strong>Figure\u00a012.28.\u00a0Receptor Types<\/strong><\/address>\n<address>(a) An ionotropic receptor is a channel that opens when the neurotransmitter binds to it. (b) A metabotropic receptor is a complex that causes metabolic changes in the cell when the neurotransmitter binds to it (1). After binding, the G protein hydrolyzes GTP and moves to the effector protein (2). When the G protein contacts the effector protein, a second messenger is generated, such as cAMP (3). The second messenger can then go on to cause changes in the neuron, such as opening or closing ion channels, metabolic changes, and changes in gene transcription.<\/address>\n<\/div>\n<div id=\"m46503-fs-id1739406\">\n<div>\n<div>\n<div>\n<div class=\"bcc-box bcc-info\">\n<h3>Interactive Link<\/h3>\n<p>Watch this\u00a0<a href=\"http:\/\/openstaxcollege.org\/l\/neurotrans\" target=\"_blank\">video<\/a>\u00a0to learn about the release of a neurotransmitter. The action potential reaches the end of the axon, called the axon terminal, and a chemical signal is released to tell the target cell to do something\u2014either to initiate a new action potential, or to suppress that activity. In a very short space, the electrical signal of the action potential is changed into the chemical signal of a neurotransmitter and then back to electrical changes in the target cell membrane. What is the importance of voltage-gated calcium channels in the release of neurotransmitters?<\/p>\n<\/div>\n<p><a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images-archive-read-only\/wp-content\/uploads\/sites\/198\/2014\/11\/20090409\/Screen-Shot-2014-11-13-at-3.17.53-PM.png\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-2514 size-full\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19152214\/Screen-Shot-2014-11-13-at-3.17.53-PM.png\" alt=\"Screen Shot 2014-11-13 at 3.17.53 PM\" width=\"578\" height=\"362\" \/><\/a><\/p>\n<\/div>\n<\/div>\n<h2 id=\"m46503-tbl-ch12_03\">Disorders of the Nervous System<\/h2>\n<div id=\"m46503-fs-id722894\">\n<div class=\"bcc-box bcc-success\">\n<div>\n<p title=\"Nervous System\">The underlying cause of some neurodegenerative diseases, such as Alzheimer\u2019s and Parkinson\u2019s, appears to be related to proteins\u2014specifically, to proteins behaving badly. One of the strongest theories of what causes Alzheimer\u2019s disease is based on the accumulation of beta-amyloid plaques, dense conglomerations of a protein that is not functioning correctly. Parkinson\u2019s disease is linked to an increase in a protein known as alpha-synuclein that is toxic to the cells of the substantia nigra nucleus in the midbrain.<\/p>\n<p>For proteins to function correctly, they are dependent on their three-dimensional shape. The linear sequence of amino acids folds into a three-dimensional shape that is based on the interactions between and among those amino acids. When the folding is disturbed, and proteins take on a different shape, they stop functioning correctly. But the disease is not necessarily the result of functional loss of these proteins; rather, these altered proteins start to accumulate and may become toxic. For example, in Alzheimer\u2019s, the hallmark of the disease is the accumulation of these amyloid plaques in the cerebral cortex. The term coined to describe this sort of disease is \u201cproteopathy\u201d and it includes other diseases. Creutzfeld-Jacob disease, the human variant of the prion disease known as mad cow disease in the bovine, also involves the accumulation of amyloid plaques, similar to Alzheimer\u2019s. Diseases of other organ systems can fall into this group as well, such as cystic fibrosis or type 2 diabetes. Recognizing the relationship between these diseases has suggested new therapeutic possibilities. Interfering with the accumulation of the proteins, and possibly as early as their original production within the cell, may unlock new ways to alleviate these devastating diseases.<\/p>\n<\/div>\n<\/div>\n<p>\u00a0<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-298\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>Anatomy &amp; Physiology. <strong>Authored by<\/strong>: OpenStax. <strong>Provided by<\/strong>: OpenStax CNX. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"http:\/\/cnx.org\/contents\/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.25\">http:\/\/cnx.org\/contents\/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.25<\/a>. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY: Attribution<\/a><\/em>. <strong>License Terms<\/strong>: Download for free at http:\/\/cnx.org\/contents\/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.25.<\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section>","protected":false},"author":17,"menu_order":6,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"Anatomy & Physiology\",\"author\":\"OpenStax\",\"organization\":\"OpenStax CNX\",\"url\":\"http:\/\/cnx.org\/contents\/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.25\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"Download for free at http:\/\/cnx.org\/contents\/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.25.\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-298","chapter","type-chapter","status-publish","hentry"],"part":23,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/298","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/users\/17"}],"version-history":[{"count":1,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/298\/revisions"}],"predecessor-version":[{"id":350,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/298\/revisions\/350"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/parts\/23"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/298\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/media?parent=298"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapter-type?post=298"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/contributor?post=298"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/license?post=298"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}