Historical overview. The calcium channel of the heart.
The present historical paper concentrates on the roots of the pharmacodynamic concept of Ca++ antagonism, and on the various therapeutic consequences of transmembrane Ca++ entry inhibition, i.e., normalization of hyperkinetic cardiac disorders, suppression of arterial and arteriolar spasms, relief of systemic arterial hypertension, stopping of cardiac dysrhythmias. Obviously in all these cases, medicine makes use of the different manifestations of one and the same fundamental action, that is to say, dose-dependent restriction of transmembrane inward Ca++ movements in active myocardium, vascular smooth muscle, or cardiac pacemaker cells. Interestingly, the origin of the principle of Ca++ antagonism and the discovery of drugs that possess Ca++-antagonistic potencies preceded the detection of the "slow Ca++ channels" by some years. However, the subsequent identification of the "slow channels" (or analogous Ca++ transport systems) as the decisive site of action of specific Ca++ antagonists has to be considered a keystone of the actual concept. The present paper does not treat tissue protection by Ca++ antagonists which is provided against intracellular Ca++ overload and its histopathological sequelae, as for instance Ca++-induced myofibrillar or mitochondrial disintegration. However, the inclusion of morphological topics, such as preservation of myocardial and vascular integrity by Ca++ antagonists, would exceed the limits of this article.
Fleckenstein
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Physiological Institute, University of Freiburg, Federal Republic of Germany.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000145:classification / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D002118:Calcium