[Effects of chlorpromazine on the skeletal muscle--a study using skinned single fibers of the guinea pig].
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.
Yoshida
K
K
First Department of Anesthesiology, Toho University School of Medicine, Tokyo.
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000209:etiology / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D002118:Calcium; D002746:Chlorpromazine