The effect of phenothiazines on Ca2+ fluxes in skeletal muscle sarcoplasmic reticulum |
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Authors: | P Volpe B Costello A Chu S Fleischer |
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Affiliation: | Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235 U.S.A. |
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Abstract: | The effect of phenothiazines (trifluoperazine, chlorpromazine, methochlorpromazine, and imipramine) on Ca2+ fluxes in light and heavy sarcoplasmic reticulum (SR) isolated from rabbit fast-twitch skeletal muscle was investigated. These drugs inhibited Ca2+ loading and (Ca2+,Mg2+)-ATPase activity, but had no effect on unidirectional Ca2+ efflux from vesicles loaded either actively or passively with Ca2+. Chlorpromazine, which is membrane permeable, and its quaternary analog, methochlorpromazine, which is membrane impermeable, gave identical results. It is concluded that (a) the enhancement of net Ca2+ release by phenothiazines is due to inhibition of Ca2+ influx mediated by the Ca2+ pump rather than to the opening of a Ca2+ channel; and (b) phenothiazines act at the outer (myoplasmic) face of the SR membrane. |
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Keywords: | To whom correspondence should be addressed. |
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