Effects of verapamil on excitation-contraction coupling in single crab muscle fibers.

Abstract

The effects of verapamil and its optical isomers on the electrical and mechanical characteristics of single muscle fibers of Callinectes danae were studied. Verapamil (10-20 microng/ml) blocked the procaine- and TEA-induced spikes; the blockade was preceded by reduction in the rate of rise of the upstroke and increase in the duration of the action potentials. Inhibition of Ba-spikes required higher concentrations of verapamil (greater than 50 microng/ml). These concentrations reduced the amplitude of the normally occurring graded electrogenic membrane responses and reduced the rate of development of the current-induced tensions. With lower concentrations (10-30 microng/ml) verapamil enhanced the negative afterpotentials and the peak amplitude of the local contractions elicited by depolarizing current pulses, while the graded membrane responses were not markedly modified. Verapamil (1-100 microng/ml) did not affect the resting membrane potential but increased the effective membrane resistance. Determination of the cable characteristics by DC pulses indicated that verapamil (1-10 microng/ml) shortens the membrane length constant, increases the specific resistivity of the sarcoplasm and, in most cases, increases the membrane time constant. Verapamil (10 microng/ml) induced tension in these crab fibers. The contractions were potentiated in Na-deficient media, by increase in [Ca]0, and by membrane depolarization; "Ca-free" salines depressed, and procaine abolished these contractions. The results suggest that verapamil affects both Ca and K conductances and interferes with the Ca-sequestering mechanisms of these fibers. The (-)-isomer of verapamil was more effective than the (+)-isomer with respect to tension development, prolongation and subsequent blockade of procaine-spikes and enhancement of current-induced after-potentials and contractions.