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Historical overview. The calcium channel of the heart
1Physiological Institute, University of Freiburg, Federal Republic of Germany.
Insights
Calcium (Ca++) antagonism, a key concept in cardiovascular medicine, involves inhibiting transmembrane Ca++ entry. This mechanism normalizes heart function, reduces spasms, lowers blood pressure, and corrects arrhythmias.
Area of Science:
- Cardiovascular Pharmacology
- Medical History
- Physiology
Background:
- The pharmacodynamic concept of Calcium (Ca++) antagonism has historical roots.
- Therapeutic applications stem from inhibiting transmembrane Ca++ entry.
- The discovery of Ca++ antagonist drugs predated the identification of slow Ca++ channels.
Purpose of the Study:
- To explore the historical origins of Ca++ antagonism.
- To detail the therapeutic outcomes of transmembrane Ca++ entry inhibition.
- To highlight the significance of slow Ca++ channels in the concept's development.
Main Methods:
- Historical review of pharmacodynamic concepts.
- Analysis of therapeutic consequences of Ca++ entry inhibition.
- Examination of the relationship between drug discovery and channel identification.
Main Results:
- Ca++ antagonism normalizes hyperkinetic cardiac disorders.
- Inhibition of Ca++ entry suppresses arterial spasms and hypertension.
- Ca++ antagonism effectively stops cardiac dysrhythmias.
- A dose-dependent restriction of transmembrane inward Ca++ movements is the fundamental action.
Conclusions:
- Ca++ antagonism is a unified principle with diverse therapeutic effects.
- Identification of slow Ca++ channels was crucial for understanding Ca++ antagonist action.
- This paper focuses on the direct effects of Ca++ antagonism, excluding tissue protection mechanisms.
Abstract:
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.