Sodium-independent inward chloride pumping in rat cardiac ventricular cells.
The intracellular Cl concentration ([Cl]i) in rat cardiac ventricular muscle, measured with double-barreled microelectrodes in vitro, was 21.3 +/- 1.5 (SD) mM [number of observations (n) = 46]. With the Na-K-Cl cotransport inhibitor bumetanide (10 microM), it fell to 13.4 +/- 1.4 mM (n = 27), and with 1 mM acetazolamide, it fell further, to 7.2 +/- 1.5 mM (n = 5), close to equilibrium with the membrane potential. In the absence of Na, [Cl]i was 15.9 +/- 1.4 mM (n = 8), and with 1 mM acetazolamide, it fell to 6.5 +/- 0.6 mM (n = 4), again close to equilibrium. The bumetanide- and Na-insensitive components of inward Cl pumping were inhibited by chlorothiazide and ethacrynic acid but were unaffected by the Na-Cl cotransport inhibitor metolazone. There was inhibition of Na-K-Cl cotransport by chlorothiazide = acetazolamide > metolazone. The anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and HCO3 had no effect on [Cl]i in any condition. Thus Cl accumulation in the rat ventricle is fully accounted for by two systems, namely, Na-K-Cl cotransport and an Na-independent, possibly primary active, process.
Chipperfield
A R
AR
Department of Anatomy and Physiology, University of Dundee, United Kingdom.
Davis
J P
JP
Harper
A A
AA
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000378:metabolism*; D004976:Ethacrynic Acid / Q000494:pharmacology; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007474:Ion Exchange; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology / Q000502:physiology*; D049992:Sodium Chloride Symporters; D027981:Symporters; D016276:Ventricular Function / Q000187:drug effects
D000838:Anions; D002352:Carrier Proteins; D002712:Chlorides; D049992:Sodium Chloride Symporters; D027981:Symporters; D012964:Sodium; D004976:Ethacrynic Acid; D000086:Acetazolamide