NaLinked Antiporter Exports Ca2 from Cardiac Muscle Cells

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 Na4

3Na4

Note that the movement of three Na+ ions is required to power the export of one Ca2+ ion from the cytosol with a [Ca2+] of «2 X 10—7 M to the extracellular medium with a [Ca2+] of 2 X 10—3 M, a gradient of some 10,000-fold. As in other muscle cells, a rise in the cytosolic Ca2+ concentration in cardiac muscle triggers contraction. By lowering cytosolic Ca2 + , operation of the Na+/Ca2+ antiporter reduces the strength of heart muscle contraction.

The Na+/K+ ATPase in the plasma membrane of cardiac 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 important, 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, inhibitors of the Na+/K+ ATPase are widely used in the treatment of congestive heart failure. I

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