Electrochemical Gradient

We have discussed simple concentration gradients—differential concentrations of a substance across a space or a membrane—but in living systems, gradients are more complex. Because cells contain proteins, most of which are negatively charged, and because ions move into and out of cells, there is an electrical gradient, 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. Thus, in a living cell, the concentration gradient and electrical gradient of Na⁺ promotes diffusion of the ion into the cell, and the electrical gradient of Na⁺ (a positive ion) tends to drive it inward to the negatively charged interior. The situation is more complex, however, for other elements such as potassium. 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, and it is especially important to muscle and nerve cells.

Moving Against a Gradient

To move substances against a concentration or an electrochemical gradient, the cell must use energy. This energy is harvested from ATP that is 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 a cell’s supply of metabolic energy may be spent maintaining these processes. Because active transport mechanisms depend on cellular metabolism for energy, they are sensitive to many metabolic poisons that interfere with the supply of ATP.

Two mechanisms exist for the transport of small-molecular weight material and macromolecules. Primary active transport moves ions across a membrane and creates a difference in charge across that membrane. The primary active transport system uses ATP to move a substance, such as an ion, into the cell, and often 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 a different number of sodium ions out of the cell ([Figure 2]). The action of this pump results in a concentration and charge difference across the membrane.

Secondary active transport describes the movement of material using the energy of the electrochemical gradient established by primary active transport. Using the energy of the electrochemical gradient created by the primary active transport system, other substances such as amino acids and glucose can be brought into the cell through membrane channels. ATP itself is formed through secondary active transport using a hydrogen ion gradient in the mitochondrion.

Endocytosis

Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different variations of endocytosis, but all share a common characteristic: The plasma membrane of the cell invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle being contained in a newly created vacuole that is formed from the plasma membrane.

Phagocytosis is the process by which large particles, such as cells, are taken in by a cell. For example, when microorganisms invade the human body, a type of white blood cell called a neutrophil removes the invader through this process, surrounding and engulfing the microorganism, which is then destroyed by the neutrophil (Figure 3]).

A variation of endocytosis is called pinocytosis. This literally means “cell drinking” and was named at a time when the assumption was that the cell was purposefully taking in extracellular fluid. In reality, this process takes in solutes that the cell needs from the extracellular fluid ([Figure 3]).

A targeted variation of endocytosis employs binding proteins in the plasma membrane that are specific for certain substances ([Figure 3]). 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 of the target of receptor-mediated endocytosis is ineffective, it will not be removed from the tissue fluids or blood. 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 (also referred to as “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

In contrast to these methods of moving material into a cell is the process of exocytosis. Exocytosis is the opposite of the processes discussed above in that its purpose is to expel material from the cell into the extracellular fluid. A particle enveloped in membrane fuses with the interior of the plasma membrane. This fusion opens the membranous envelope to the exterior of the cell, and the particle is expelled into the extracellular space ([Figure 4]).