17.4: Active Transport

Excitability (adaptation) is another of the defining properties of life. This property of all cells is based on chemical and electrical reactivity. Neurotransmitters released at a synapse cross the synaptic cleft from a “sending” neuron to a responding cell (another neuron or a muscle cell). The neurotransmitter binds to receptors on the responding cell resulting in a membrane depolarization, a rapid change in electrical potential difference across the cell membrane. While responses to neurotransmitters occur in fractions of a second, all kinds of cells are responsive, albeit not always as fast as neurons or muscle cells.

Changes in the membrane polarity of any cell depend on unequal concentrations of ions inside and outside cells. These ionic differences across membranes enable all cells, but especially neurons and muscle cells, to respond to chemical and other (e.g., electrical) signals. Thus, cells have a resting potential due to a higher [\(\rm K^{+}\)] in the cytosol and higher [\(\rm Cl^{−}\)] and [\(\rm Na^{+}\)] outside the cell. The measured resting potential (difference in charge or potential difference) of most cells is typically between −50 mv to −70 mv, negative because negative (i.e., \(\rm Cl^{−}\)) ions are at higher concentration inside the cell than outside. Such ion concentration gradients permit physiological response to chemical or other signals. They change when cells are excited when they (quite normally) leak ions. Whether incidental or intentional, the correct ion balance must be restored to maintain excitability. Relative concentrations of \(\rm K^{+}\), \(\rm Cl^{−}\), and \(\rm Na^{+}\) ions accounting for a cell’s resting potential are shown in Figure 17.8.

Figure 17.8: The resting potential of a cell results from an ion-concentration imbalance across the plasma membrane. Sodium and chloride ion concentrations are higher inside cells while potassium ion levels are higher outside the cell. Thus, the cytoplasm is slightly negative compared to the extracellular fluid.

Maintaining a cell’s resting potential requires energy, and this is accomplished by the ATP-dependent \(\rm Na^{+}\) /\(\rm K^{+}\) pump, an active-transport protein complex. Follow the allosteric changes as the \(\rm Na^{+}\)/\(\rm K^{+}\) pump (Figure 17.9 below) works to restore ion gradients.

Figure 17.9: After a change in the resting potential (e.g., depolarization) of a cell, \(\rm Na^{+}\) /\(\rm K^{+}\) ion balance across the cell membrane is restored by an ATP-powered sodium/potassium pump. Three \(\rm Na^{+}\) ions are pumped out of the cell for every two \(\rm K^{+}\) ions that enter the cell.

In operation, the ATPase domain of the \(\rm Na^{+}\) /\(\rm K^{+}\) pump protein hydrolyzes ATP, leaving a phosphate attached to the pump and inducing the first of several allosteric changes in the pump proteins (step 1 in the illustration). In its new conformation, the pump binds three Na+ ions, causing a second conformational change that in turn releases the \(\rm Na^{+}\) ions into the extracellular fluid (step 2). The release of \(\rm Na^{+}\) ions outside the cell causes a third allosteric change (step 3), after which two \(\rm K^{+}\) ions from the extracellular fluid can bind to the pump protein. \(\rm K^{+}\) binding causes the hydrolysis of the phosphate from the pump protein, returning it to its original conformation (step 4) and releasing the two \(\rm K^{+}\) ions into the cytosol. The \(\rm Na^{+}\) /\(\rm K^{+}\) pump is ready for action again!

295 Potassium Leakage Helps Maintain Cellular Resting Potentials

296 Active Transport by the Sodium/Potassium Pump

For his discovery of the ATPase-powered sodium/potassium pump and his studies of how it works to maintain intracellular ion balance, Jens C. Skou earned a share of the Nobel Prize in Chemistry in 1997. Read more at 1997 Chemistry Nobel prize-Skou.