Abstract
‘Calcium-antagonists’ are a group of pharmacological agents which are potent vasodilators and are clinically used for the treatment of angina. They are thought to block Ca2+ channels in vascular smooth muscle1,2 and myocardium3–5 but other sites of action have been proposed6. These agents bind tightly to heart muscle and suppress action potential and contraction. Nifedipine and nisoldipine (BAY K 5552) are Ca2+ antagonists which have o-nitrobenzyl groups and are photolabile7. We have found that short pulses of UV light rapidly inactivate these drugs in ventricular muscle. This observation allowed us to study the effect of Ca2+ antagonists on action potential, Ca2+ current and tension in conditions in which diffusion of those drugs from their site of action was not rate limiting. Our studies, described here, suggest that the primary mechanism of action of Ca2+ antagonists is the blockade of the Ca2+ channel and support the idea that extracellular space is the immediate source of contractile Ca2+ in the frog heart.
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References
Bolton, T. B. Physiol. Rev. 59, 606–718 (1979).
Meisheri, K. D., Hwang, O. & Van Breeman, C. J. Membrane Biol. 59, 19–25 (1981).
Coraboeuf, E. The Slow Inward Current and Cardiac Arrhythmias, Ch. 3 (Martinus Nijhoff, Boston, 1980).
Henry, P. D. Am J. Cardiol. 46, 1047–1058 (1980).
Fleckenstein, A. New Perspectives on Calcium Antagonists, Ch. 5 (Williams & Wilkins, Baltimore, 1981).
Millard, R. W. et al. Am. J. Cardiol. 49, 499–506 (1982).
Schlossmann, V. K. Arzneim.-Forsch. (Drug Res.) 22, 60–62 (1972).
Morad, M. & Orkand, R. J. Physiol., Lond. 219, 167–189 (1971).
Morad, M. & Goldman, Y. Prog. Biophys. molec. Biol. 27, 257–313 (1973).
Goldman, Y. & Morad, M. J. Physiol., Lond. 268, 613–654 (1977).
Morrison, H. A. The Chemistry of the Nitro and Nitroso Groups Pt 1 (ed. Feuer, H.) 165–213 (Wiley, New York, 1969).
Kaplan, J. H., Forbush, B. III & Hoffman, J. F. Biochemistry 17, 1929–1935 (1978).
McCray, J. A., Herbette, L., Kihara, T. & Trentham, D. R. Proc. natn. Acad. Sci. U.S.A. 77, 7237–7241 (1980).
Morad, M. & Klitzner, T. Biophysical Aspects of Cardiac Muscle (ed. Morad, M.) 1227–1243 (Academic, New York, 1978).
Kohlhardt, M., Bauer, B., Krause, A. & Fleckenstein, A. Pflügers Arch. ges. Physiol. 338, 115–123 (1973).
Kohlhardt, M., Mnich, Z. & Haap, K. J. molec. cell. Cardiol. 11, 1227–1243 (1979).
Babskii, E. B. & Donskikh, E. A. Doklady Akademii Naak. SSSK 178, 248–251 (1968).
Morad, M., Tung, L. & Greenspan, A. M. Am. J. Cardiol. 49, 595–601 (1982).
Ishizuka, T. & Endo, M. Circulation Res. 52, Suppl. 1, 110–114 (1983).
Nayler, W. G. & Grinwald, P. Fedn Proc. 40, 2855–2861 (1981).
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Morad, M., Goldman, Y. & Trentham, D. Rapid photochemical inactivation of Ca2+-antagonists shows that Ca2+ entry directly activates contraction in frog heart. Nature 304, 635–638 (1983). https://doi.org/10.1038/304635a0
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DOI: https://doi.org/10.1038/304635a0
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