Coupling excitation-contraction, slow

Cardiac muscle is highly dependent on calcium influx for normal function. Impulse generation in the sinoatrial node and conduction in the atrioventricular node—so-called slow-response, or calcium-dependent, action potentials—may be reduced or blocked by all of the calcium channel blockers. Excitation-contraction coupling in all cardiac cells requires calcium influx, so these drugs reduce cardiac contractility in a dose-dependent fashion. In some cases, cardiac output may also decrease. This reduction in cardiac mechanical function is another mechanism by which the calcium channel blockers can reduce the oxygen requirement in patients with angina. 

The maintenance of physiologic calcium concentrations in the intracellular and extracellular spaces is vital for the preservation and function of cell membranes propagation of neuromuscular activity regulation of endocrine and exocrine secretory functions blood coagulation cascade platelet adhesion process bone metabolism muscle cell excitation/contraction coupling and mediation of the elec-trophysiologic slow-channel response in cardiac and smooth-muscle tissue. 

Cardiac Muscle. Calcium inhibitory agents may interfere with excitation-contraction coupling processes in myocardial or vascular smooth muscle cells by a number of mechanisms including l) inhibition of the slow inward current through direct competition for slow channels or interference with the membrane binding of Ca2+ 2) interference with the release... 

Ca " is a critical cation necessary for cardiac function in terms of automaticity/ pacemaker activity, conduction of electrical signals, and excitation-contraction coupling of myocytes. Drugs and chemicals that influence Ca flux in cardiac tissue also have a profound effect on the electrical and mechanical function of the heart. The slow Ca " current is mediated, in part, via the voltage-gated L-type Ca channels, one that can be influenced by Ca channel antagonists such as verapamil, D600, and diltiazem. Cardiac toxicity associated with the blockade of this channel can result in the disruption of rhythm and rate, as well as contraction and relaxation, of the heart. 

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