CHLORIDE CHANNEL BLOCKERS INHIBIT CA2-MUSCLE SARCOPLASMIC-RETICULUM( UPTAKE BY THE SMOOTH)

Despite the fact that Ca2+ transport into the sarcoplasmic reticulum ( SR) of muscle cells is electrogenic, a potential difference is not mai ntained across the SR membrane. To achieve electroneutrality, compensa tory charge movement must occur during Ca2+ uptake. To examine the rol e of Cl- in this charge movement in smooth muscle cells, Ca2+ transpor t into the SR of saponin-permeabilized smooth muscle cells was measure d in the presence of various Cl- channel blockers or when l(-), Br-, o r SO42- was substituted for Cl-. Calcium uptake was inhibited in a dos e-dependent manner by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NP PB) and by indanyioxyacetic acid 94 (R(+)-IAA-94), but not by niflumic acid or 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). Smooth musc le SR Ca2+ uptake was also partially inhibited by the substitution of SO42- for Cl-, but not when Cl- was replaced by l(-) or Br-. Neither N PPB nor R(+)-IAA-94 inhibited Ca2+ uptake into cardiac muscle SR vesic les at concentrations that maximally inhibited uptake in smooth muscle cells. These results indicate that Cl- movement is important for char ge compensation in smooth muscle cells and that the Cl- channel or cha nnels involved are different in smooth and cardiac muscle cells.