Calmodulin, Ca²⁺-Antagonists and Ca²⁺-Transporters in Nerve and Muscle

Summary

Calcium is of fundamental importance in the regulation of both muscle contraction and neurosecretion. Its control of these processes is achieved by its binding and activation of various Ca²⁺-binding proteins (CBP), including those in the Ca²⁺ channel, the Na⁺-Ca²⁺ antiporter, and intracellular calmodulin (CDR). Generally, Ca²⁺-binding to regulatory CBP exposes hydrophobic sites on their surface at which the CBP interfaces with its receptor or binds inhibitory hydrophobic ligands. We find that some Ca²⁺-antagonist drugs (Ca-ANT) bind to and inhibit calmodulin and that some calmodulin antagonists (CDR-ANT) block Ca²⁺ channels. This suggests that CDR and the CBP that regulate the Ca²⁺ channel may be quite homologous proteins. Ca-ANT and CDR-ANT are not effective inhibitors of the Na⁺-Ca²⁺ antiporters of heart sarcolemma and brain synaptosomes, suggesting that these antiporters are fundamentally different from the antiporter of heart mitochondria. These results are discussed in terms of Ca²⁺-binding proteins being potential targets for pharmacological interventions designed to block specific aspects of the action of calcium.