The effect of phenothiazines on Ca2+ fluxes in skeletal muscle sarcoplasmic reticulum.

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.

journal_name

Arch Biochem Biophys

authors

Volpe P,Costello B,Chu A,Fleischer S

doi

10.1016/0003-9861(84)90614-3

subject

Has Abstract

pub_date

1984-08-15 00:00:00

pages

174-9

issue

1

eissn

0003-9861

issn

1096-0384

pii

0003-9861(84)90614-3

journal_volume

233

pub_type

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