Calcium, Cell Membrane, and Excitation-Contraction Coupling

Abstract

Skeletal muscle, heart muscle, and smooth muscle differ with respect to morphology, function, and Ca metabolism. For the actual coupling between excitation and contraction, three different sources of Ca2+ supply are conceivable: release from intracellular organelles, release from plasmalemmal binding sites, and transmembranous influx. Considerable experimental evidence favors the membranes of the sarcoplasmic reticulum as the source of coupling Ca2+ in skeletal muscle, whereas in cardiac and smooth muscles the Ca store from which coupling Ca2+ is released has to be in intimate contact with the extracellular Ca2+ concentration. In order to distinguish between the two remaining possibilities for the source of coupling Ca2+, i.e., transmembranous Ca influx and Ca release from the plasmalemma, Ca antagonist--widely accepted tools for detecting Ca influx--were used. Ca antagonists did not have any influence on Ca exchange or Ca uptake either in cardiac or in smooth muscles. These findings may be interpreted as follows: Ca antagonists do not act by inhibiting the Ca2+ influx, although they reduce the amount of coupling Ca2+. This conclusion conflicts with current ideas concerning the mode of action of Ca antagonists. We feel, however, that the experimental support for the Ca-channel hypothesis is rather vague. This leads us to favor the plasmalemma as the main source of coupling Ca2+ in cardiac and smooth muscles.