Abstract
Phorbol esters have marked effects on voltage-dependent Ca2+ channels1. Inhibitory2 and stimulatory3 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.
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Lacerda, A., Rampe, D. & Brown, A. Effects of protein kinase C activators on cardiac Ca2+ channels. Nature 335, 249–251 (1988). https://doi.org/10.1038/335249a0
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DOI: https://doi.org/10.1038/335249a0
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