title: Calmodulin, Ca2+-antagonists and Ca2+-transporters in nerve and muscle.
abstract: 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.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002642:Chick Embryo; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D013552:Swine; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D019831:Sodium-Calcium Exchanger; D002118:Calcium