The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma

Experiments with adenosine 5'-[gamma-thio]triphosphate have shown that the activating treatment is mediated by a kinase and the deactivating treatment by a phosphatase, and the concerted operation of the two enzymes is made possible by their different Ca2+ affinity.

Abstract

The Na+/Ca2+-exchange of calf-heart sarcolemma is activated by a treatment with ATP, Mg2+, and Ca2+, and deactivated by a treatment with phosphorylase phosphatase. The effect of the latter can be substituted by a treatment with Mg2+, Ca2+, and calmodulin. The activating treatment does not require added calmodulin, but is inhibited by calmodulin antagonists. Evidently, endogenous calmodulin is required and sufficient. Activation is half-maximal at about 2 microM Ca2+. Added calmodulin, however, decreases the Km (Ca2+) of the activating process to about 0.8 microM. Deactivation is half-maximal, at optimal calmodulin concentrations, at about 1.5 microM Ca2+. Experiments with adenosine 5'-[gamma-thio]triphosphate have shown that the activating treatment is mediated by a kinase and the deactivating treatment by a phosphatase. The concerted operation of the two enzymes is made possible by their different Ca2+ affinity. At saturating Ca2+ concentrations, the level of ATP may also influence the balance of the two enzymes.