Role of extracellular calcium on heart muscle energetics: effects of verapamil

Abstract

The mechanical and energetic effects of verapamil (VER) and reduction of extracellular Ca concentration ([Ca]o) were studied in the interventricular rabbit septa and the dog papillary muscle. Even though the negative inotropic effects of VER [i.e., decrease in developed tension (T), maximal rates of contraction (+T) and relaxation (-T), and tension time integral] qualitatively resemble [Ca]o reduction, VER also elicited an anti-relaxant effect (decrease in -T/T and prolongation of the last phase of relaxation) that was not found with [Ca]o reduction. Resting heat production was similar in both preparations and remained unaffected either by changes in [Ca]o or by the presence of VER. The ratio between T and active heat production per beat (H'a) under constant fiber length decreased with VER, and this decreased economy of contraction was more marked with the increase in contraction frequency. Conversely, the T/H'a remained unaltered with changes in [Ca]o. Tension-independent heat decreased in the presence of VER and, although muscle economy can be improved by increasing muscle length in a VER-treated muscle, it is not possible to achieve either the maximal T or the maximal contraction economy that can be obtained by stretching a nontreated muscle. It may be concluded that at constant fiber length and frequency of contraction VER decreases myocardial contractile force, impairs relaxation, and decreases contraction economy. Neither the mechanical nor the energetic effects of VER can be explained solely on the basis of a reduced extracellular Ca availability, so that either the density of the Ca that enters through the channel is different from that of other sources of Ca or VER has an effect on the cross-bridge cycling mechanism.