Rapid photochemical inactivation of Ca2+-antagonists shows that Ca2+ entry directly activates contraction in frog heart
- 1 August 1983
- journal article
- Published by Springer Nature in Nature
- Vol. 304 (5927), 635-638
- https://doi.org/10.1038/304635a0
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 muscle and myocardium but other sites of action have been proposed. 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 photolabile. 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.Keywords
This publication has 11 references indexed in Scilit:
- Differential cardiovascular effects of calcium channel blocking agents: Potential mechanismsThe American Journal of Cardiology, 1982
- Evidence for two separate Ca2+ pathways in smooth muscle plasmalemmaThe Journal of Membrane Biology, 1981
- Comparative pharmacology of calcium antagonists: Nifedipine, verapamil and diltiazemThe American Journal of Cardiology, 1980
- A new approach to time-resolved studies of ATP-requiring biological systems; laser flash photolysis of caged ATP.Proceedings of the National Academy of Sciences, 1980
- Mechanisms of action of transmitters and other substances on smooth muscle.Physiological Reviews, 1979
- Rapid photolytic release of adenosine 5'-triphosphate from a protected analog: utilization by the sodium:potassium pump of human red blood cell ghostsBiochemistry, 1978
- Measurement of transmembrane potential and current in cardiac muscle: a new voltage clamp method.The Journal of Physiology, 1977
- Excitation-contraction coupling in heart muscle: Membrane control of development of tensionProgress in Biophysics and Molecular Biology, 1973
- Selective inhibition of the transmembrane Ca conductivity of mammalian myocardial fibres by Ni, Co and Mn ionsPflügers Archiv - European Journal of Physiology, 1973
- Excitation—contraction coupling in frog ventricle: evidence from voltage clamp studiesThe Journal of Physiology, 1971