Inhibition of excitation-contraction coupling by a Ca channel blocker nicardipine at low temperature in frog twitch fibers.

Abstract

Effects of a Ca channel blocker, nicardipine, on excitation-contraction (E-C) coupling were investigated in single twitch fibers dissected from short skeletal muscles of the frog, Rana japonica. The treatment with 20 microM nicardipine at 25 degrees C evoked a reversible twitch potentiation. By contrast, the treatment at the same concentration at 5 degrees C for 30 min evoked an intense twitch inhibition. The inhibition was irreversible. This paralyzed fiber remained at nearly normal resting and propagated action potentials. The treatment with 30 microM nicardipine for 14 min at 6 degrees C completely inhibited a potassium contracture by 190 mEq/l potassium ion for 1.5 h after the removal of nicardipine despite the retention of normal resting potentials. The paralyzed fiber which was previously treated with 20 microM nicardipine for 30 min at 6 degrees C, also remained at normal action potential and at partial potassium contracture, and responded to 3 mM caffeine stimulation with a normal contracture. Dose-dependence curves obtained from the data on the treatments with nicardipine at various concentrations for 30 min at 6 degrees C consisted of an opposite sigmoidal shape with both threshold and half maximum inhibition at 1 and 1.5 microM for twitch and similarly at 5 and 12 microM for potassium contracture. Temperature-dependence curves obtained from the data on the treatments with 20 microM nicardipine for 30 min at various temperatures consisted of a sigmoidal shape with half maximum inhibition at 15 degrees C for twitch and at 12 degrees C for potassium contracture. A working hypothesis "two component-three state model" for E-C coupling was proposed based on the interpreted mechanism of nicardipine action.