Abstract
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.
Highlights
Ca2+ channels incardiac and skeletal muscle are known to be regulated by cyclic AMP [6,7,8]
Activationof protein kinase C by diacylglycerol or phorbol esters has been associated with modifications in calcium currents in nonmuscle cells [14,15,16,17]
Inthis study I have shown that activation of protein kinase C enhanced both the number of dihydropyridine receptors and the dihydropyridine-sensitive Ca2+ uptakein embryonic culturedskeletal musclecells
Summary
Q 1987 by The American Society of Biological Chemists, Inc. Vol 262, No 10, Issue of April 5 , pp. 4649-4652 1987 Printed in ii.S.A. 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. Activationof protein kinase C (the Ca2+/phospholipid-dependent enzyme) by diacylglycerol or phorbol esters has been associated with modifications in calcium currents in nonmuscle cells [14,15,16,17]. Inthis study I have shown that activation of protein kinase C enhanced both the number of dihydropyridine receptors and the dihydropyridine-sensitive Ca2+ uptakein embryonic culturedskeletal musclecells. These data provide evidence that diacylglycerol is a physiological messenger mediating probably an agonist-induced regulation of calcium channels in skeletalmuscle
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