Chapter 11: Transmembrane Transport of Ions and Small Molecules

A Na⁺-Linked Ca²⁺ Antiporter Regulates the Strength of Cardiac Muscle Contraction

In all muscle cells, a rise in the cytosolic Ca²⁺ concentration triggers contraction. In cardiac muscle cells, a three-Na⁺/one-Ca²⁺ antiporter, rather than the plasma-membrane Ca²⁺ ATPase discussed earlier, plays the principal role in maintaining a low concentration of Ca²⁺ in the cytosol. The transport reaction mediated by this cation antiporter can be written

3 Na⁺_out + Ca _in²⁺ ⇌ 3 Na⁺_in + Ca²⁺_out

Note that the inward movement of three Na⁺ ions is required to power the export of one Ca²⁺ ion from the cytosol, which has a [Ca²⁺] of ~2 × 10⁻⁷ M, to the extracellular medium, which has a [Ca²⁺] of ~2 × 10⁻³ M—a concentration gradient of some 10,000-fold (higher on the outside). By lowering cytosolic Ca²⁺, operation of the Na⁺/Ca²⁺ antiporter reduces the strength of heart muscle contraction.

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The Na⁺/K⁺ ATPase in the plasma membrane of cardiac muscle cells, as in other body cells, creates the Na⁺ concentration gradient necessary for export of Ca²⁺ by the Na⁺-linked Ca²⁺ antiporter. As mentioned earlier, inhibition of the Na⁺/K⁺ ATPase by the drugs ouabain and digoxin lowers the cytosolic K⁺ concentration and, more importantly here, simultaneously increases cytosolic Na⁺. The resulting reduced Na⁺ electrochemical gradient across the membrane causes the Na⁺-linked Ca²⁺ antiporter to function less efficiently. As a result, fewer Ca²⁺ ions are exported, and the cytosolic Ca²⁺ concentration increases, causing the muscle to contract more strongly. Because of their ability to increase the force of heart muscle contractions, drugs such as ouabain and digoxin that inhibit the Na⁺/K⁺ ATPase are widely used in the treatment of congestive heart failure.

A Na+-Linked Ca2+ Antiporter Regulates the Strength of Cardiac Muscle Contraction

A Na⁺-Linked Ca²⁺ Antiporter Regulates the Strength of Cardiac Muscle Contraction