[Effects of chlorpromazine on the skeletal muscle--a study using skinned single fibers of the guinea pig]

Abstract

Chlorpromazine (CPZ) was reported to influence the functions of the sarcoplasmic reticulum (SR). To determine the action sites of CPZ on calcium functions in skeletal muscle, the calcium-induced calcium release (CICR) rates from SR, Ca2+ uptake rates into the SR, and Ca2+ sensitivity to the contractile system were examined using the single skinned fiber. CPZ enhanced slightly rates of CICR in a dose-dependent manner. The Ca2+ uptake rates into the SR were significantly attenuated at the concentrations of 10 and 30 microM of CPZ. CPZ in a concentration below 10 microM did not affect Ca2+ uptake rates. This agent did not enhance Ca2+ sensitivity of the contractile system. Although CPZ was suggested to increase Ca2+ release from the SR by Takagi, this observation might have resulted from either the increase of Ca2+ release or the inhibition of Ca2+ uptake since Ca2+ might be pumped up to the SR during the release of Ca2+ in his experimental conditions. Endo's method enabled us to analyze these functions independently. CPZ was found to act mainly on the inhibition of Ca2+ uptake and not to increase Ca2+ release from the SR in a concentration of CPZ (10 microM). These results suggest that CPZ may induce the increase of intracellular Ca2+ concentration. CPZ may be safely employed to MH susceptible patients, since CPZ at a clinical concentration showed no influence on Ca2+ related functions of the skeletal muscle.