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 20μM nicardipine at 25°C evoked a reversiblé twitch potentiation. By contrast, the treatment at the same concentration at 5°C for 30min evoked an intense twitch inhibition. The inhibition was irreversible. This paralyzed fiber remained at nearly normal resting and propagated action potentials. The treatment with 30μM nicardipine for 14min at 6°C completely inhibited a potassium contracture by 190mEq/l potassium ion for 1.5h after the removal of nicardipine despite the retention of normal resting potentials. The paralyzed fiber which was previously treated with 20μM nicardipine for 30min at 6°C, also remained at normal action potential and at partial potassium contracture, and responded to 3mM caffeine stimulation with a normal contracture. Dose-dependence curves obtained from the data on the treatments with nicardipine at various concentrations for 30min at 6°C consisted of an opposite sigmoidal shape with both threshold and half maximum inhibition at 1 and 1.5μM for twitch and similarly at 5 and 12μM for potassium contracture. Temperature-dependence curves obtained from the data on the treatments with 20μM nicardipine for 30min at various temperatures consisted of a sigmoidal shape with half maximum inhibition at 15°C for twitch and at 12°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.
