Modulation of [3H]dihydropyridine receptors by activation of protein kinase C in chick muscle cells.
Modulation of ion channels is an essential step for understanding the regulation of cellular functions. 1,4-Dihydropyridines (nitrendipine, nifedipine, PN 200-110, etc.) are potent inhibitors of voltage-dependent calcium channels and are important therapeutic agents in the treatment of various cardiovascular disorders such as angina and cardiac arrhythmias. In this work a new procedure is employed to determine the density of surface dihydropyridine receptors in contracting muscle cells in culture. Activation of endogenous protein kinase C (the Ca2+/phospholipid-dependent enzyme) by the tumor promoter phorbol-12-myristate or 1-oleoyl-2-acetylglycerol enhanced the number of dihydropyridine receptors without significant change in the receptor affinity. The increase in the number of receptors was associated with stimulation of the dihydropyridine-sensitive 45Ca uptake as well as activation of protein kinase C in myotubes treated with phorbol esters. These data strongly suggest that activation of protein kinase C promotes the appearance of dihydropyridine receptors in the plasma membrane.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels; D002478:Cells, Cultured; D002642:Chick Embryo; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004075:Diglycerides; D007473:Ion Channels; D011978:Receptors, Nicotinic; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium