Chloride channel blockers inhibit Ca2+ uptake by the smooth muscle sarcoplasmic reticulum.
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.
Pollock
N S
NS
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Kargacin
M E
ME
Kargacin
G J
GJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D006016:Glycolates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009130:Muscle, Smooth / Q000502:physiology*; D009579:Nitrobenzoates / Q000494:pharmacology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D013270:Stomach / Q000502:physiology*
D018118:Chloride Channels; D006016:Glycolates; D009579:Nitrobenzoates; D013267:Stilbenes; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C015765:MK 473; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; D002118:Calcium