The specific ionic composition of the cytosol usually differs greatly from that of the surrounding extracellular fluid. In virtually all cells—including microbial, plant, and animal cells—the cytosolic pH is kept near 7.2 regardless of the extracellular pH. In the most extreme case, there is a 1-million-fold difference in H⁺ concentration between the cytosol of the epithelial cells lining the stomach and the stomach contents after a meal. Furthermore, the cytosolic concentration of K⁺ is much higher than that of Na⁺. In both invertebrates and vertebrates, the concentration of K⁺ is 20–40 times higher in the cytosol than in the blood, while the concentration of Na⁺ is 8–12 times lower in the cytosol than in the blood (Table 11-2).

Some Ca²⁺ in the cytosol is bound to the negatively charged groups in ATP and in proteins and other molecules, but it is the concentration of unbound (or “free”) Ca²⁺ that is critical to its functions in signaling pathways and muscle contraction. The concentration of free Ca²⁺ in the cytosol is generally less than 0.2 micromolar (2 × 10⁻⁷ M), a thousand or more times lower than that in the blood. Plant cells and many microorganisms maintain similarly high cytosolic concentrations of K⁺ and low concentrations of Ca²⁺ and Na⁺, even if the cells are cultured in very dilute salt solutions.

The ion pumps discussed in this section are largely responsible for establishing and maintaining the usual ionic gradients across the plasma and intracellular membranes. In carrying out this task, cells expend considerable energy. For example, up to 25 percent of the ATP produced by nerve and kidney cells is used for ion transport, and human erythrocytes consume up to 50 percent of their available ATP for this purpose; in both cases, most of this ATP is used to power the Na⁺/K⁺ pump (see Figure 11-3). The resultant Na⁺ and K⁺ gradients in neurons are essential for their ability to conduct electrical signals rapidly and efficiently, as we detail in Chapter 22. Certain enzymes required for protein synthesis in all cells require a high K⁺ concentration and are inhibited by high concentrations of Na⁺; these enzymes would cease to function without the operation of the Na⁺/K⁺ pump. In cells treated with poisons that inhibit the production of ATP (e.g., 2,4-dinitrophenol in aerobic cells), the pumping stops, and the ion concentrations inside the cell gradually approach those of the exterior environment as ions spontaneously move through channels in the plasma membrane down their electrochemical gradients. Eventually the treated cells die, partly because protein synthesis requires a high concentration of K⁺ ions and partly because, in the absence of a Na⁺ gradient across the plasma membrane, a cell cannot import certain nutrients such as amino acids (see Figure 11-3). Studies on the effects of such poisons provided early evidence for the existence and significance of ion pumps.

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