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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References
Janis, R. A., Silver, R. J. & Triggle, D. J. Adv. Drug Res. 16, 309–591 (1987).
Leatherman, G. F., Kim, D. & Smith, T. W. Am. J. Physiol. 253, H205–H209 (1987).
Dösemeci, A., Dhallan, R. S., Cohen, N. M., Lederer, W. J. & Rogers, T. B. Circulation Res. 62, 347–357 (1988).
DeRiemer, S. A., Strong, J. A., Albert, K. A., Greengard, P. & Kaczmarek, L. K. Nature 313, 313–316 (1985).
Hess, P., Lansman, J. B. & Tsien, R. W. J. gen. Physiol. 88, 293–319 (1986).
Reuter, H., Stevens, C. F., Tsien, R. W. & Yellen, G. Nature 297, 501–504 (1982).
Cavalié, A., Pelzer, D. & Trautwein, W. Pflüegers Arch. ges. Physiol. 406, 241–258 (1986).
Cavalié, A., Ochi, R., Pelzer, D. & Trautwein, W. Pflüegers Arch. ges. Physiol. 398, 284–297 (1983).
Strong, J. A., Fox, A. P., Tsien, R. W. & Kaczmarek, L. K. Nature 325, 714–717 (1987).
Carbone, E. & Lux, H. D. J. Physiol. 386, 571–601 (1987).
Yoshimasa, T., Sibley, D. R., Bouvier, M., Lefkowitz, R. J. & Caron, M. G. Nature 327, 67–70 (1987).
Trautwein, W., Cavalié, A., Flockerzi, V., Hofmann, F. & Pelzer, D. Circulation Res. 61, 17–23 (1987).
Tsien, R. W. et al. J. molec cell. Cardiol. 18, 691–710 (1986).
Shenolikar, S., Karbon, C. W. & Enna, S. J. Biochem. biophys. Res. Commun. 139, 251–258 (1986).
Teutsch, I., Beer, W., Frisch, G., Weible, A. & Ruoff, H. J. Archs Pharmacol. 377, R61 (1988).
Nastainczyk, W. et al. Eur. J. Biochem. 169, 137–142 (1987).
Matthies, H. J. G., Palfrey, H. C., Hirning, L. D. & Miller, R. J. J. Neurosci. 7, 1198–1206 (1987).
Kreutter, D., Caldwell, A. B. & Morin, M. J. J. Biol. Chem. 260, 5979–5984 (1985).
Mark, G. E. & Strasser, F. F. Exp Cell Res. 44, 217–233 (1966).
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. J. biol. Chem. 193, 265–275 (1951).
Kunze, D. L., Lacerda, A. E., Wilson, D. L. & Brown, A. M. J. gen. Physiol. 86, 691–719 (1985).
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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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