Impulse Conduction

Learning Objectives

  • Distinguish the major functions of the nervous system: sensation, integration, and response
  • Describe the components of the membrane that establish the resting membrane potential
  • Describe the changes that occur to the membrane that result in the action potential applying the terms polarized, depolarized, and repolarized.
  • Describe the process of propagation in a myelinated neuron and an unmyelinated neuron.
  • Explain how neurotransmitters are used in neuron communication.

Having looked at the components of nervous tissue, and the basic anatomy of the nervous system, next comes an understanding of how nervous tissue is capable of communicating within the nervous system. Before getting to the nuts and bolts of how this works, an illustration of how the components come together will be helpful. An example is summarized in Figure 8.7.

This diagram shows the complete pathway a nerve impulse takes when a person tests the temperature of shower water with their hand. First, a sensory nerve ending in the index finger sends a nerve impulse to the spinal cord. A cross section of one segment of the vertebrae is shown from a superior view. The sensory nerve connected to the nerve ending is located in the dorsal root ganglion. The nerve ending is a dendrite of the sensory neuron, as it also has an axon that synapses with an interneuron. The interneuron then synapses with a second interneuron in the thalamus. This second interneuron synapses with brain tissue in the cerebral cortex, allowing conscious perception of the water temperature. The brain then initiates a motor command by stimulating an upper motor neuron in the cerebral cortex. The axon of the upper motor neuron extends all the way to the spinal cord, where it synapses with a lower motor neuron in the gray matter of the spinal cord. The impulse then travels down the lower motor neuron back to the hand where it synapses with the skeletal muscles of the hand. This triggers the muscle contractions that turn the dials of the shower to adjust the water temperature.
Figure 8.7. Testing the Water
(1) The sensory neuron has endings in the skin that sense a stimulus such as water temperature. The strength of the signal that starts here is dependent on the strength of the stimulus. (2) The graded potential from the sensory endings, if strong enough, will initiate an action potential at the initial segment of the axon (which is immediately adjacent to the sensory endings in the skin). (3) The axon of the peripheral sensory neuron enters the spinal cord and contacts another neuron in the gray matter. The contact is a synapse where another graded potential is caused by the release of a chemical signal from the axon terminals. (4) An action potential is initiated at the initial segment of this neuron and travels up the sensory pathway to a region of the brain called the thalamus. Another synapse passes the information along to the next neuron. (5) The sensory pathway ends when the signal reaches the cerebral cortex. (6) After integration with neurons in other parts of the cerebral cortex, a motor command is sent from the precentral gyrus of the frontal cortex. (7) The upper motor neuron sends an action potential down to the spinal cord. The target of the upper motor neuron is the dendrites of the lower motor neuron in the gray matter of the spinal cord. (8) The axon of the lower motor neuron emerges from the spinal cord in a nerve and connects to a muscle through a neuromuscular junction to cause contraction of the target muscle.
 
 

Imagine you are about to take a shower in the morning before going to school. You have turned on the faucet to start the water as you prepare to get in the shower. After a few minutes, you expect the water to be a temperature that will be comfortable to enter. So you put your hand out into the spray of water. What happens next depends on how your nervous system interacts with the stimulus of the water temperature and what you do in response to that stimulus.

Found in the skin of your fingers or toes is a type of sensory receptor that is sensitive to temperature, called a thermoreceptor. When you place your hand under the shower (Figure 8.8), the cell membrane of the thermoreceptors changes its electrical state (voltage). The amount of change is dependent on the strength of the stimulus (how hot the water is). This is called a graded potential. If the stimulus is strong, the voltage of the cell membrane will change enough to generate an electrical signal that will travel down the axon. You have learned about this type of signaling before, with respect to the interaction of nerves and muscles at the neuromuscular junction. The voltage at which such a signal is generated is called the threshold, and the resulting electrical signal is called an action potential. In this example, the action potential travels—a process known as propagation—along the axon from the axon hillock to the axon terminals and into the synaptic end bulbs. When this signal reaches the end bulbs, it causes the release of a signaling molecule called a neurotransmitter.

This diagram shows the first step of the previous figure. A hand is placed under flowing water, causing a sensory receptor in the index finger to send a nerve impulse down the arm, to the spinal cord.
Figure 8.8. The Sensory Input
Receptors in the skin sense the temperature of the water.
 

The neurotransmitter diffuses across the short distance of the synapse and binds to a receptor protein of the target neuron. When the molecular signal binds to the receptor, the cell membrane of the target neuron changes its electrical state and a new graded potential begins. If that graded potential is strong enough to reach threshold, the second neuron generates an action potential. The target of this neuron is another neuron in the thalamus of the brain, the part of the CNS that acts as a relay for sensory information. At another synapse, neurotransmitter is released and binds to its receptor. The thalamus then sends the sensory information to the cerebral cortex, the outermost layer of gray matter in the brain, where conscious perception of that water temperature begins.

Within the cerebral cortex, information is processed among many neurons, integrating the stimulus of the water temperature with other sensory stimuli, with your emotional state (you just aren’t ready to wake up; the bed is calling to you), memories (perhaps of the lab notes you have to study before a quiz). Finally, a plan is developed about what to do, whether that is to turn the temperature up, turn the whole shower off and go back to bed, or step into the shower. To do any of these things, the cerebral cortex has to send a command out to your body to move muscles (Figure 8.9).  All of this occurs in a fraction of a second, but this story is the basis of how the nervous system functions.

This diagram shows the later steps of Figure 12.13. A hand is placed under flowing water. The axon of a motor neuron travels down the forearm and then branches as it reaches the hand. Each branch synapses with a different skeletal muscle in the hand. The synapse between the axon branches and the muscle is a neuromuscular junction. An impulse travelling down the motor neuron will cause the skeletal muscles to contract, resulting in muscle movement. In this case, the movement results in the person adjusting the faucet dials to change the temperature of the water.
Figure 8.9. The Motor Response
On the basis of the sensory input and the integration in the CNS, a motor response is formulated and executed.

Electrically Active Cell Membranes

The functions of the nervous system—sensation, integration, and response—depend on the functions of the neurons underlying these pathways. To understand how neurons are able to communicate, it is necessary to describe the role of an excitable membrane in generating these signals. The basis of this communication is the action potential, which demonstrates how changes in the membrane can constitute a signal. Looking at the way these signals work in more variable circumstances involves a look at graded potentials, which will be covered in the next section.

Most cells in the body make use of charged particles, ions, to build up a charge across the cell membrane. Previously, this was shown to be a part of how muscle cells work. For skeletal muscles to contract there must be input from a neuron. Both of the cells make use of the cell membrane to regulate ion movement between the extracellular fluid and cytosol.

As you learned in the chapter on cells, the cell membrane is primarily responsible for regulating what can cross the membrane and what stays on only one side. The cell membrane is a phospholipid bilayer, so only substances that can pass directly through the hydrophobic core can diffuse through unaided. Charged particles, which are hydrophilic by definition, cannot pass through the cell membrane without assistance (Figure 8.10). Transmembrane proteins, specifically channel proteins, make this possible. Several channels, as well as specialized energy dependent “ion-pumps,” are necessary to generate a transmembrane potential and to generate an action potential. Of special interest is the carrier protein referred to as the sodium/potassium pump that moves sodium ions (Na+) out of a cell and potassium ions (K+) into a cell, thus regulating ion concentration on both sides of the cell membrane.

This diagram shows a cross section of a cell membrane. The cell membrane proteins are large, blocky, objects. Peripheral proteins are not embedded in the phospholipid bilayer. The peripheral protein shown here is attached to the outside surface of another protein on the extracellular fluid side. Integral proteins are embedded between the phospholipids of the cell membrane. The transmembrane integral protein extends through both phospholipids layers. The opposite ends of this protein project into the cytosol and the extracellular fluid. A second, smaller integral protein only extends into the inner phospholipid layer. Its opposite end projects into the cytosol. This second protein is, therefore, not a transmembrane protein. The channel protein is cylinder shaped with a hollow internal tube labeled the pore. The sides of the channel protein can bulge inward to close the pore.
Figure 8.10. Cell Membrane and Transmembrane Proteins
The cell membrane is composed of a phospholipid bilayer and has many transmembrane proteins, including different types of channel proteins that serve as ion channels.
 

The sodium/potassium pump requires energy in the form of adenosine triphosphate (ATP), so it is also referred to as an ATPase. As was explained in the cell chapter, the concentration of Na+ is higher outside the cell than inside, and the concentration of K+ is higher inside the cell is higher than outside. That means that this pump is moving the ions against the concentration gradients for sodium and potassium, which is why it requires energy. In fact, the pump basically maintains those concentration gradients.

Ion channels do not always freely allow ions to diffuse across the membrane. They are opened by certain events, meaning the channels are gated.  Channels can be categorized on the basis of how they are gated. Although these classes of ion channels are found primarily in cells of nervous or muscular tissue, they also can be found in cells of epithelial and connective tissues.  A ligand-gated channel opens because a signaling molecule, a ligand, binds to the extracellular region of the channel and opens the gated channel (Figure 8.11).

These two diagrams each show a channel protein embedded in the cell membrane. In the left diagram, there is a large number of sodium ions (NA plus) and calcium ions (CA two plus) in the extracellular fluid. Within the cytosol, there is a large number of potassium ions (K plus) but only a few sodium ions. In this diagram, the channel is closed. Two ACH molecules are floating in the extracellular fluid. Their label indicates that a neurotransmitter, a ligand, is required to open the ion channel. The neurotransmitter receptor site on the extracellular fluid side of the channel protein matches the shape of the ACH molecules. In the right diagram, the two ACH molecules attach to the neurotransmitter receptor sites on the channel protein. This opens the channel and the sodium and calcium ions diffuse through the channel and into the cytosol, down their concentration gradient. The potassium ions also diffuse through the channel in the opposite direction down their concentration gradient (out of the cell and into the extracellular fluid).
Figure 8.11. Ligand-Gated Channels
When the ligand, in this case the neurotransmitter acetylcholine, binds to a specific location on the extracellular surface of the channel protein, the pore opens to allow select ions through. The ions, in this case, are cations of sodium, calcium, and potassium.
 
 A mechanically gated channel opens because of a physical distortion of the cell membrane. Many channels associated with the sense of touch (somatosensation) are mechanically gated. For example, as pressure is applied to the skin, these channels open and allow ions to enter the cell. Similar to this type of channel would be the channel that opens on the basis of temperature changes, as in testing the water in the shower (Figure 8.12).
These two diagrams each show a channel protein embedded in the cell membrane. In the left diagram, there are a large number of sodium ions in the extracellular fluid, but only a few sodium ions in the cytosol. There is a large number of calcium ions in the cytosol but only a few calcium ions in the extracellular fluid. In this diagram, the channel is closed, as the extracellular side has a lid, somewhat resembling that on a trash can, that is closed over the channel opening. In the right diagram, the mechanically gated channel is open. This allows the sodium ions to flow from the extracellular fluid into the cell, down their concentration gradient. At the same time, the calcium ions are moving from the cytosol into the extracellular fluid, down their concentration gradient.
Figure 8.12. Mechanically Gated Channels
When a mechanical change occurs in the surrounding tissue, such as pressure or touch, the channel is physically opened. Thermoreceptors work on a similar principle. When the local tissue temperature changes, the protein reacts by physically opening the channel.
 

voltage-gated channel is a channel that responds to changes in the electrical properties of the membrane in which it is embedded. Normally, the inner portion of the membrane is at a negative voltage. When that voltage becomes less negative, the channel begins to allow ions to cross the membrane (Figure 8.13).

This is a two part diagram. Both diagrams show a voltage gated channel embedded in the lipid membrane bilayer. The channel contains a sphere shaped gate that is attached to a filament. In the first diagram there are several ions in the cytosol but only one ion in the extracellular fluid. The voltage across the membrane is currently minus seventy millivolts and the voltage gated channel is closed. In the second diagram, the voltage in the cytosol is minus fifty millivolts. This voltage change has caused the voltage gated channel to open, as the small sphere is no longer occluding the channel. One of the ions is moving through the channel, down its concentration gradient, and out into the extracellular fluid.
Figure 8.13. Voltage-Gated Channels
Voltage-gated channels open when the transmembrane voltage changes around them. Amino acids in the structure of the protein are sensitive to charge and cause the pore to open to the selected ion.
 

leakage channel is randomly gated, meaning that it opens and closes at random, hence the reference to leaking. There is no actual event that opens the channel; instead, it has an intrinsic rate of switching between the open and closed states. Leakage channels contribute to the resting transmembrane voltage of the excitable membrane (Figure 8.14).

This is a two part diagram. Both diagrams show a leakage channel embedded in the lipid membrane bilayer. The leakage channel is cylindrical with a large, central opening. In the first diagram there are several ions in the cytosol but only one ion in the extracellular fluid. No ions are moving through the leakage channel because the channel is closed. In the second diagram, the leakage channel randomly opens, allowing two ions to travel through the channel, down their concentration gradient, and out into the extracellular fluid.
Figure 8.14. Leakage Channels
In certain situations, ions need to move across the membrane randomly. The particular electrical properties of certain cells are modified by the presence of this type of channel.
 

The Membrane Potential

The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking (Figure 8.15).

This diagram shows a cross section of a cell membrane. The extracellular fluid side of the cell membrane is positively charged while the cytosol side of the membrane is negatively charged. There is a microelectrode embedded in the cell membrane. The microelectrode is attached to a voltmeter, which also has a reference electrode on the extracellular fluid side. The readout of the voltmeter is negative 70 millivolts.
Figure 8.15. Measuring Charge across a Membrane with a Voltmeter
A recording electrode is inserted into the cell and a reference electrode is outside the cell. By comparing the charge measured by these two electrodes, the transmembrane voltage is determined. It is conventional to express that value for the cytosol relative to the outside.

The concentration of ions in extracellular and intracellular fluids is largely balanced, with a net neutral charge. However, a slight difference in charge occurs right at the membrane surface, both internally and externally. It is the difference in this very limited region that has all the power in neurons (and muscle cells) to generate electrical signals, including action potentials.

Before these electrical signals can be described, the resting state of the membrane must be explained. When the cell is at rest, and the ion channels are closed (except for leakage channels which randomly open), ions are distributed across the membrane in a very predictable way. The concentration of Na+ outside the cell is greater than the concentration inside. Also, the concentration of K+ inside the cell is greater than outside. The cytosol contains a high concentration of anions, in the form of phosphate ions and negatively charged proteins. Large anions are a component of the inner cell membrane, including specialized phospholipids and proteins associated with the inner leaflet of the membrane (leaflet is a term used for one side of the lipid bilayer membrane). The negative charge is localized in the large anions.

With the ions distributed across the membrane at these concentrations, the difference in charge is measured at -70 mV, the value described as the resting membrane potential. The exact value measured for the resting membrane potential varies between cells, but -70 mV is most commonly used as this value. This voltage would actually be much lower except for the contributions of some important proteins in the membrane. Leakage channels allow Na+ to slowly move into the cell or K+ to slowly move out, and the Na+/K+ pump restores them. This may appear to be a waste of energy, but each has a role in maintaining the membrane potential.

The Action Potential

Resting membrane potential describes the steady state of the cell, which is a dynamic process that is balanced by ion leakage and ion pumping. Without any outside influence, it will not change. To get an electrical signal started, the membrane potential has to change.

This starts with a channel opening for Na+ in the membrane. Because the concentration of Na+ is higher outside the cell than inside the cell, ions will rush into the cell that are driven largely by the concentration gradient. Because sodium is a positively charged ion, it will change the relative voltage immediately inside the cell relative to immediately outside. The resting potential is the state of the membrane at a voltage of -70 mV, so the sodium cation entering the cell will cause it to become less negative. This is known as depolarization, meaning the membrane potential moves toward zero.

The concentration gradient for Na+ is so strong that it will continue to enter the cell even after the membrane potential has become zero, so that the voltage immediately around the pore begins to become positive. The electrical gradient also plays a role, as negative proteins below the membrane attract the sodium ion. The membrane potential will reach +30 mV by the time sodium has entered the cell.

As the membrane potential reaches +30 mV, other voltage-gated channels are opening in the membrane. These channels are specific for the potassium ion. A concentration gradient acts on K+, as well. As K+ starts to leave the cell, taking a positive charge with it, the membrane potential begins to move back toward its resting voltage. This is called repolarization, meaning that the membrane voltage moves back toward the -70 mV value of the resting membrane potential.

Repolarization returns the membrane potential to the -70 mV value that indicates the resting potential, but it actually overshoots that value. Potassium ions reach equilibrium when the membrane voltage is below -70 mV, so a period of hyperpolarization occurs while the K+ channels are open. Those K+ channels are slightly delayed in closing, accounting for this short overshoot.

What has been described here is the action potential, which is presented as a graph of voltage over time in Figure 8.16. It is the electrical signal that nervous tissue generates for communication. The change in the membrane voltage from -70 mV at rest to +30 mV at the end of depolarization is a 100-mV change. That can also be written as a 0.1-V change. To put that value in perspective, think about a battery. An AA battery that you might find in a television remote has a voltage of 1.5 V, or a 9-V battery (the rectangular battery with two posts on one end) is, obviously, 9 V. The change seen in the action potential is one or two orders of magnitude less than the charge in these batteries. In fact, the membrane potential can be described as a battery. A charge is stored across the membrane that can be released under the correct conditions. A battery in your remote has stored a charge that is “released” when you push a button.

This graph has membrane potential, in millivolts, on the X axis, ranging from negative 70 to positive thirty. Time is on the X axis. The plot line starts steadily at negative seventy and then increases to negative 55 millivolts. The plot line then increases quickly, peaking at positive thirty. This is the depolarization phase. The plot line then quickly drops back to negative seventy millivolts. This is the repolarization phase. The plot line continues to drop but then gradually increases back to negative seventy millivolts. The area where the plot line is below negative seventy millivolts is the hyperpolarization phase.
Figure 8.16. Graph of Action Potential
Plotting voltage measured across the cell membrane against time, the action potential begins with depolarization, followed by repolarization, which goes past the resting potential into hyperpolarization, and finally the membrane returns to rest.

What happens across the membrane of an electrically active cell is a dynamic process that is hard to visualize with static images or through text descriptions. View this animation to learn more about this process. What is the difference between the driving force for Na+ and K+? And what is similar about the movement of these two ions?

The question is, now, what initiates the action potential? The description above conveniently glosses over that point. But it is vital to understanding what is happening. The membrane potential will stay at the resting voltage until something changes. The description above just says that a Na+ channel opens. Now, to say “a channel opens” does not mean that one individual transmembrane protein changes. Instead, it means that one kind of channel opens. There are a few different types of channels that allow Na+ to cross the membrane. A ligand-gated Na+ channel will open when a neurotransmitter binds to it and a mechanically gated Na+ channel will open when a physical stimulus affects a sensory receptor (like pressure applied to the skin compresses a touch receptor). Whether it is a neurotransmitter binding to its receptor protein or a sensory stimulus activating a sensory receptor cell, some stimulus gets the process started. Sodium starts to enter the cell and the membrane becomes less negative.

A third type of channel that is an important part of depolarization in the action potential is the voltage-gated Na+ channel. The channels that start depolarizing the membrane because of a stimulus help the cell to depolarize from -70 mV to -55 mV. Once the membrane reaches that voltage, the voltage-gated Na+ channels open. This is what is known as the threshold. Any depolarization that does not change the membrane potential to -55 mV or higher will not reach threshold and thus will not result in an action potential. Also, any stimulus that depolarizes the membrane to -55 mV or beyond will cause a large number of channels to open and an action potential will be initiated.

Because of the threshold, the action potential can be likened to a digital event—it either happens or it does not. If the threshold is not reached, then no action potential occurs. If depolarization reaches -55 mV, then the action potential continues and runs all the way to +30 mV, at which K+ causes repolarization, including the hyperpolarizing overshoot. Also, those changes are the same for every action potential, which means that once the threshold is reached, the exact same thing happens. A stronger stimulus, which might depolarize the membrane well past threshold, will not make a “bigger” action potential. Action potentials are “all or none.” Either the membrane reaches the threshold and everything occurs as described above, or the membrane does not reach the threshold and nothing else happens. All action potentials peak at the same voltage (+30 mV), so one action potential is not bigger than another. Stronger stimuli will initiate multiple action potentials more quickly, but the individual signals are not bigger. Thus, for example, you will not feel a greater sensation of pain, or have a stronger muscle contraction, because of the size of the action potential because they are not different sizes.

Propagation of the Action Potential

The action potential is initiated at the beginning of the axon, at what is called the initial segment. There is a high density of voltage-gated Na+ channels so that rapid depolarization can take place here. Going down the length of the axon, the action potential is propagated because more voltage-gated Na+ channels are opened as the depolarization spreads. This spreading occurs because Na+ enters through the channel and moves along the inside of the cell membrane. As the Na+ moves, or flows, a short distance along the cell membrane, its positive charge depolarizes a little more of the cell membrane. As that depolarization spreads, new voltage-gated Na+ channels open and more ions rush into the cell, spreading the depolarization a little farther.

Because voltage-gated Na+ channels are inactivated at the peak of the depolarization, they cannot be opened again for a brief time. Because of this, depolarization spreading back toward previously opened channels has no effect. The action potential must propagate toward the axon terminals; as a result, the polarity of the neuron is maintained, as mentioned above.

Propagation, as described above, applies to unmyelinated axons. When myelination is present, the action potential propagates differently. Sodium ions that enter the cell at the initial segment start to spread along the length of the axon segment, but there are no voltage-gated Na+ channels until the first node of Ranvier. Because there is not constant opening of these channels along the axon segment, the depolarization spreads at an optimal speed. The distance between nodes is the optimal distance to keep the membrane still depolarized above threshold at the next node. As Na+ spreads along the inside of the membrane of the axon segment, the charge starts to dissipate. If the node were any farther down the axon, that depolarization would have fallen off too much for voltage-gated Na+ channels to be activated at the next node of Ranvier. If the nodes were any closer together, the speed of propagation would be slower.

Propagation along an unmyelinated axon is referred to as continuous conduction; along the length of a myelinated axon, it is saltatory conduction. Continuous conduction is slow because there are always voltage-gated Na+ channels opening, and more and more Na+ is rushing into the cell. Saltatory conduction is faster because the action potential basically jumps from one node to the next (saltare = “to leap”), and the new influx of Na+ renews the depolarized membrane. Along with the myelination of the axon, the diameter of the axon can influence the speed of conduction. Much as water runs faster in a wide river than in a narrow creek, Na+-based depolarization spreads faster down a wide axon than down a narrow one. This concept is known as resistance and is generally true for electrical wires or plumbing, just as it is true for axons, although the specific conditions are different at the scales of electrons or ions versus water in a river.

Neurotransmitter Release

When an action potential reaches the axon terminals, voltage-gated Ca2+ channels in the membrane of the synaptic end bulb open. The concentration of Ca2+ increases inside the end bulb, and the Ca2+ ion associates with proteins in the outer surface of neurotransmitter vesicles. The Ca2+ facilitates 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 synaptic cleft.

Once in the synaptic cleft, the neurotransmitter diffuses the short distance to the postsynaptic membrane of the next neuron and interacts with neurotransmitter receptors on the dendrites or cell body. 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 (Figure 8.17).

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.
Figure 8.17. The Synapse
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 Ca2+ enters 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.

 

Homeostatic Imbalances: Potassium Concentration

Glial cells, especially astrocytes, are responsible for maintaining the chemical environment of the CNS tissue. The concentrations of ions in the extracellular fluid are the basis for how the membrane potential is established and changes in electrochemical signaling. If the balance of ions is upset, drastic outcomes are possible.

Normally the concentration of K+ is higher inside the neuron than outside. After the repolarizing phase of the action potential, K+ leakage channels and the Na+/K+ pump ensure that the ions return to their original locations. Following a stroke or other ischemic event, extracellular K+ levels are elevated. The astrocytes in the area are equipped to clear excess K+ to aid the pump. But when the level is far out of balance, the effects can be irreversible.

Astrocytes can become reactive in cases such as these, which impairs their ability to maintain the local chemical environment. The glial cells enlarge and their processes swell. They lose their K+ buffering ability and the function of the pump is affected, or even reversed. If a Na+ gradient breaks down, this has a more important effect than interrupting the action potential. Glucose transport into cells is coupled with Na+ co-transport. When that is lost, the cell cannot get the energy it needs. In the central nervous system, carbohydrate metabolism is the only means of producing ATP. Elsewhere in the body, cells rely on carbohydrates, lipids, or amino acids to power mitochondrial ATP production. But the CNS does not store lipids in adipocytes (fat cells) as an energy reserve. The lipids in the CNS are in the cell membranes of neurons and glial cells, notably as an integral component of myelin. Proteins in the CNS are crucial to neuronal function, in roles such as channels for electrical signaling or as part of the cytoskeleton. Those macromolecules are not used to power mitochondrial ATP production in neurons.

Disorders of the Nervous System

The underlying cause of some neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, appears to be related to proteins—specifically, to proteins behaving badly. One of the strongest theories of what causes Alzheimer’s disease is based on the accumulation of beta-amyloid plaques, dense conglomerations of a protein that is not functioning correctly. Parkinson’s 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.

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’s, 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 “proteopathy” 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’s. 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.

 

Interactive Link

Visit this site to see a virtual neurophysiology lab, and to observe electrophysiological processes in the nervous system, where scientists directly measure the electrical signals produced by neurons. Often, the action potentials occur so rapidly that watching a screen to see them occur is not helpful. A speaker is powered by the signals recorded from a neuron and it “pops” each time the neuron fires an action potential. These action potentials are firing so fast that it sounds like static on the radio. Electrophysiologists can recognize the patterns within that static to understand what is happening. Why is the leech model used for measuring the electrical activity of neurons instead of using humans?