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Biophys J, October 1998, p. 1759-1766, Vol. 75, No. 4

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

N. S. Pollock, M. E. Kargacin, and G. J. Kargacin

Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1, Canada

Despite 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.

Biophys J, October 1998, p. 1759-1766, Vol. 75, No. 4
© 1998 by the Biophysical Society   0006-3495/98/10/1759/08  $2.00


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