Electrochemical Gradient

Figure 1. Electrochemical gradients arise from the combined effects of concentration gradients and electrical gradients. (credit: modification of work by “Synaptitude”/Wikimedia Commons)

We have discussed simple concentration gradient, differential concentrations of a substance across a space or a membrane.  In living systems, gradients are more complex. Cells contain proteins, most of which are negatively charged.  Ions move into and out of cells creating  a difference of charge across the plasma membrane. The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed.  At the same time, cells have higher concentrations of potassium (K⁺) and lower concentrations of sodium (Na⁺) than does the extracellular fluid. The concentration gradient and electrical gradient of Na⁺ promotes diffusion of the ion into the cell, and the electrical gradient of Na⁺ tends to drive it inward to the negatively charged interior. The situation gets more complex.  The electrical gradient of K⁺ promotes diffusion of the ion into the cell, but the concentration gradient of K⁺ promotes diffusion out of the cell (Figure 1). The combined gradient that affects an ion is called its electrochemical gradient.  It is especially important to muscle and nerve cells.

Moving Against a Gradient

To move substances against a concentration or electrochemical gradient, the cell must use energy. This energy is harvested from ATP  generated through cellular metabolism. Active transport mechanisms, collectively called pumps or carrier proteins, work against electrochemical gradients. With the exception of ions, small substances constantly pass through plasma membranes. Active transport maintains concentrations of ions and other substances needed by living cells in the face of these passive changes.  Much of the ATP a cell uses goes to maintaining these processes.   Because active transport mechanisms depend on cellular metabolism for energy, they are sensitive to anything that interferes with the supply of ATP.

Two mechanisms are involved with active transport.  Primary active transport moves ions across a membrane and creates a difference in charge across the membrane. The primary active transport system uses ATP to move a substance into the cell and at the same time, a second substance is moved out of the cell. The sodium-potassium pump, an important pump in animal cells, expends energy to move potassium ions into the cell and sodium ions out of the cell (Figure 2). The action of this pump results in a concentration and charge difference across the membrane.

Figure 2. The sodium-potassium pump move potassium and sodium ions across the plasma membrane. (credit: modification of work by Mariana Ruiz Villarreal)

Secondary active transport describes the movement of material using the energy of the electrochemical gradient established by primary active transport. Using that energy, other substances can be brought into the cell through membrane channels. ATP itself is formed through secondary active transport in the mitochondrion.  Cells that undergo active transport have higher numbers of mitochondria in order to make the necessary ATP.

Endocytosis

Endocytosis is a type of active transport that moves particles, cellular parts, and even whole cells.  Different variations of endocytosis exist but all share a common characteristic, invagination.  The plasma membrane of the cell invaginates, folds in, forming a pocket around the target particle. The pocket pinches off creating a vacuole/vesicle from the plasma membrane surrounding the target particle.   A great deal of ATP is required for endocytosis due to the tremendous manipulation of the plasma membrane.

Phagocytosis(“cell-eating”) is the process by which large particles are taken in by a cell. For example, when microorganisms invade the human body, a neutrophil, a type of white blood cell, removes the invader through endocytosis.  The neutrophil then destroys the invader (Figure 3a).

A variation of endocytosis is called pinocytosis(“cell-drinking).   This process allows the cell to take in solutes needed from the extracellular fluid (Figure 3b).

Figure 3. Three variations of endocytosis are shown. (a) In one form of endocytosis, phagocytosis, the cell membrane surrounds the particle and pinches off to form an intracellular vacuole. (b) In another type of endocytosis, pinocytosis, the cell membrane surrounds a small volume of fluid and pinches off, forming a vesicle. (c) In receptor-mediated endocytosis, uptake of substances by the cell is targeted to a single type of substance that binds at the receptor on the external cell membrane. (credit: modification of work by Mariana Ruiz Villarreal)

A targeted variation of endocytosis employs binding proteins in the plasma membrane that are specific for certain substances (Figure 3c). The particles bind to the proteins and the plasma membrane invaginates, bringing the substance and the proteins into the cell. If passage across the membrane is ineffective, it will not be removed.  Instead, it will stay in those fluids and increase in concentration. Some human diseases are caused by a failure of receptor-mediated endocytosis. For example, the form of cholesterol termed low-density lipoprotein or LDL (“bad” cholesterol) is removed from the blood by receptor-mediated endocytosis. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood, because their cells cannot clear the chemical from their blood.

Exocytosis

Figure 4. In exocytosis, a vesicle migrates to the plasma membrane, binds, and releases its contents to the outside of the cell. (credit: modification of work by Mariana Ruiz Villarreal)

In contrast to these methods of moving material into a cell is the process of exocytosis. Exocytosis seeks to expel material from the cell into the extracellular fluid. A particle enveloped in a membrane fuses with the interior of the plasma membrane. This fusion opens the membranous envelope to the exterior of the cell.  The particle is expelled into the extracellular space (Figure 4).  Since the plasma membrane is being manipulated, a great deal of ATP is necessary.

Section Summary

The combined gradient that affects an ion includes its concentration gradient and its electrical gradient. Living cells need certain substances in concentrations greater than they exist in the extracellular space. Moving substances up their electrochemical gradients requires energy from the cell. Active transport uses energy stored in ATP to fuel the transport. Active transport uses integral proteins in the cell membrane to move the material.  These proteins are analogous to a pump. Some pumps, which carry out primary active transport, couple directly with ATP to drive their action. In secondary transport, energy from primary transport can be used to move another substance into the cell and up its concentration gradient.

Endocytosis methods require the direct use of ATP to fuel the transport of large particles, cellular parts, or whole cells to be engulfed by other cells in a process called phagocytosis. In phagocytosis, a portion of the membrane invaginates and flows around the particle, eventually pinching off and leaving the particle wholly enclosed by an envelope of plasma membrane. Pinocytosis is a similar process on a smaller scale. The cell expels waste and other particles through the reverse process, exocytosis. Wastes are moved outside the cell, pushing a membranous vesicle to the plasma membrane, allowing the vesicle to fuse with the membrane and incorporating itself into the membrane structure, releasing its contents to the exterior of the cell.