Movement of acid equivalents across the mammalian smooth muscle cell membrane.
Factors affecting intracellular pH (pHi) in the smooth muscle of guinea pig ureter have been investigated using pH-sensitive microelectrodes. Associated acids and bases appear to have free passage across the cell membrane but results suggest very low permeability to charged acid equivalents, thus implicating carrier-mediated movements in many of the observed pHi transients. Recovery from acidosis in the nominal absence of CO2 was inhibited by removal of Na+ and by the presence of amiloride, indicating that Na+/H+ exchange was responsible. The presence of CO2 resulted in a faster recovery from acidosis but, since intracellular buffering power was not increased, not a substantially faster effective extrusion of protons. Surprisingly, amiloride no longer caused discernable inhibition. Recovery from moderate acidosis remained Na+ dependent but was not inhibited by DIDS or acetazolamide or by the absence of Cl-, suggesting a dominant Na+-, and HCO3(-)-dependent mechanism unlike any hitherto described. Recovery from alkalosis was inhibited by DIDS and Cl(-)-free conditions, indicating that Cl-/HCO3- exchange was involved. Results suggest reversal of this mechanism on extreme acidosis. Experiments in vascular smooth muscle with fluorescent indicators confirm the presence of Na+/H+ exchange but provide conflicting evidence about the presence and properties of the HCO3(-)-dependent mechanism.
Aickin
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CC
University Department of Pharmacology, Oxford.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers; D014513:Ureter
D001639:Bicarbonates; D002352:Carrier Proteins; D002712:Chlorides; D011522:Protons; D000644:Quaternary Ammonium Compounds; D017923:Sodium-Hydrogen Exchangers; D002245:Carbon Dioxide; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000584:Amiloride; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid