Effects of protein kinase C activators on cardiac Ca2+ channels.
Phorbol esters have marked effects on voltage-dependent Ca2+ channels. Inhibitory and stimulatory effects on cardiac Ca2+ channels have been attributed in both cases to activation of protein kinase C. We show that the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate stimulates dihydropyridine-sensitive 45Ca2+ influx in primary cultures of neonatal rat ventricular myocytes within 5 s, but that after a 20-min pre-incubation period the phorbol ester markedly inhibits 45Ca2+ influx. The sequence of stimulation followed by inhibition is confirmed in cell-attached patch clamp recordings of single Ca2+ channel currents. The stimulatory effect is faster at 0 mV than at -40 mV, leading to the novel conclusion that the rate of protein kinase C activation is modulated by the state of the Ca2+ channel.
Lacerda
A E
AE
Department of Physiology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Rampe
D
D
Brown
A M
AM
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006352:Heart Ventricles; D007473:Ion Channels / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007473:Ion Channels; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium