Chloride channel blockers inhibit Ca2+ uptake by the smooth muscle sarcoplasmic reticulum

Biophys J. 1998 Oct;75(4):1759-66. doi: 10.1016/S0006-3495(98)77617-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Chloride Channels / antagonists & inhibitors*
  • Glycolates / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Muscle, Smooth / physiology*
  • Nitrobenzoates / pharmacology*
  • Rabbits
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism*
  • Stilbenes / pharmacology
  • Stomach / physiology*


  • Chloride Channels
  • Glycolates
  • Nitrobenzoates
  • Stilbenes
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • MK 473
  • 4,4'-dinitro-2,2'-stilbenedisulfonic acid
  • Calcium