Chloride Channel Blockers Inhibit Ca2+ Uptake by the Smooth Muscle Sarcoplasmic Reticulum

AbstractDespite the fact that Ca2+ transport into the sarcoplasmic reticulum (SR) of muscle cells is electrogenic, a potential difference is not maintained across the SR membrane. To achieve electroneutrality, compensatory charge movement must occur during Ca2+ uptake. To examine the role of Cl− in this charge movement in smooth muscle cells, Ca2+ transport into the SR of saponin-permeabilized smooth muscle cells was measured in the presence of various Cl− channel blockers or when I−, Br−, or SO42− was substituted for Cl−. Calcium uptake was inhibited in a dose-dependent manner by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and by indanyloxyacetic acid 94 (R(+)-IAA-94), but not by niflumic acid or 4,4′-dinitrostilbene-2,2′-disulfonic acid (DNDS). Smooth muscle SR Ca2+ uptake was also partially inhibited by the substitution of SO42− for Cl−, but not when Cl− was replaced by I− or Br−. Neither NPPB nor R(+)-IAA-94 inhibited Ca2+ uptake into cardiac muscle SR vesicles at concentrations that maximally inhibited uptake in smooth muscle cells. These results indicate that Cl− movement is important for charge compensation in smooth muscle cells and that the Cl− channel or channels involved are different in smooth and cardiac muscle cells