The Sodium Pump

For some time, the model in Figure 4-6b was thought to be an accurate description of real animal cells. The difficulty with this scheme arose when it became apparent that real cells are permeable to sodium, while the model cell is assumed to be impermeable to sodium. Permeability to sodium, however, would be catastrophic for the model cell. If sodium can cross the membrane, then all extracellular solutes can cross the membrane. Recall from Chapter 3, however, what happens to cells that are placed in ECF containing only permeant solutes (like the urea example in Figure 3-4c): the cell swells and bursts. The cornerstone of the strategy employed by animal cells to achieve osmotic balance is that the cell membrane must exclude an extracellular solute to balance the impermeant organic solutes inside the cell. Sodium ions played that role for the model cell of Figure 4-6b.

How can the permeability of the plasma membrane to sodium be reconciled with the requirement for osmotic balance? An answer to this question was suggested by the experiments that demonstrated the sodium permeability of the cell membrane in the first place. In these experiments, red blood cells were incubated in an external medium containing radioactive sodium ions. When the cells were removed from the radioactive medium and washed thoroughly, it was found that they remained radioactive, indicating that the cells had taken up some of the radioactive sodium. This showed that the plasma membrane was permeable to sodium. In addition, it was found that the radioactive cells slowly lost their radioactive sodium when incubated in normal ECF. This latter observation was surprising because both the concentration gradient and the electrical gradient for sodium are directed inward; neither would tend to move sodium out of the cell. Further, the rate of this loss of radioactive sodium from the cell interior was slowed dramatically by cooling the cells, indicating that a source of energy other than simple diffusion was being tapped to actively "pump" sodium out of the cell against its concentrational and electrical gradients. It turns out that this energy source is metabolic energy in the form of the high-energy phosphate compound adenosine triphosphate (ATP).

This active pumping of sodium out of the cell effectively prevents sodium from accumulating intracellularly as it leaks in down its concentration and electrical gradients. Thus, even though sodium can cross the membrane, it is actively extruded at a rate sufficiently high to counterbalance the inward leak. The net result is that sodium behaves osmotically as though it cannot cross the membrane. Note however that this mechanism is fundamentally different from the situation in the model cell of Figure 4-6b. The model was in equilibrium and required no energy input to maintain itself. By contrast, real animal cells are in a finely balanced steady state, in which there is no net movement of ions across the cell membrane, but which requires the expenditure of metabolic energy.

Metabolic inhibitors, such as cyanide or dinitrophenol, prevent the pumping of sodium out of the cell and cause cells to gain sodium and swell. If ATP is added, the pump can operate once again and the accumulated sodium will be extruded. Similarly, other manipulations that reduce the rate of ATP production, like cooling, cause sodium accumulation and increased cell volume. Experiments of this type demonstrated the role of ATP in the active extrusion of sodium and the maintenance of cell volume. The mechanism of the sodium pump has been studied biochemically. The pump itself is a particular kind of membrane-associated protein molecule that can bind both sodium ions and ATP at the intracellular face of the membrane. The protein then acts as an enzyme to cleave one of the high-energy phosphate bonds of the ATP molecule, using the released energy to drive the bound sodium out across the membrane by a process that is not yet completely understood.

The action of the sodium pump also requires potassium ions in the ECF. Binding of K+ to a part of the protein on the outer surface of the cell membrane is required for the protein to return to the configuration in which it can again bind another ATP and sodium ions at the inner surface of the membrane. The potassium bound on the outside is released again on the inside of the cell, so that the protein molecule acts as a bidirectional pump carrying sodium out across the membrane and potassium in. Thus, the sodium pump is more correctly referred to as the sodium-potassium pump, and can be thought of as a shuttle carrying Na+ out across the membrane, releasing it in the ECF, then carrying K+ in across the membrane and releasing it in the ICF. Because the pump molecule splits ATP and binds both sodium and potassium ions, biochemists refer to this membrane-associated enzyme as a Na+/K+ ATPase.

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