Increase in intrinsic anion conductance upon inhibition of the electroneutral Cl(-)/HCO(3)(-) exchanger: effect of CO(2)/HCO(3)(-).
The electroneutral Cl(-)/HCO(3)(-) exchange, present at the apical membrane of rabbit gallbladder epithelium, apparently is converted into a stilbene- and dipyridamole-sensitive, nonrectifying, approximately 5-pS anion channel after the exchange is directly inhibited (inhibitors tested: hydrochlorothiazide (HCTZ), phlorizin, phenylglyoxal and diphenylamine-2-carboxylic acid (DPC)). In intact tissue, in the absence of CO(2)/HCO(3)(-) in the media, the opening of these channels causes an approximately 7-mV depolarization of the apical membrane. This has been shown to be a constant index of the total Cl(-) conductance (G(Cl)) activated. The effect of exogenous and endogenous CO(2)/HCO(3)(-) on the depolarization has now been investigated in the intact tissue by conventional microelectrodes. The anion exchange has been measured radiochemically. The presence of exogenous or endogenous CO(2)/HCO(3)(-) reduces the depolarization induced by HCTZ, phlorizin and DPC from approximately 7 to 3 mV, but 10(-4) mol/l acetazolamide restores the full depolarization. Response time, S(0.5) and Hill number are unchanged in each case. The way of bicarbonate replacement is irrelevant. The depolarization generated by phenylglyoxal, which covalently binds to the transport site of the exchanger and prevents HCO(3)(-) binding, is unaffected by CO(2)/HCO(3)(-) presence. HCO(3)(-) binding to the transport site is suggested to partially hinder the conversion of the exchanger into the channel.
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Dipartimento di Fisiologia e Biochimica Generali, Sezione di Fisiologia Generale, Università degli Studi di Milano,Via Celoria 26, I-20133 Milan, Italy. fistrasp@mailserver.unimi.it
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D000818:Animals; D000838:Anions / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D027963:Chloride-Bicarbonate Antiporters / Q000037:antagonists & inhibitors* / Q000502:physiology; D002713:Chlorine / Q000493:pharmacokinetics*; D004553:Electric Conductivity; D004594:Electrophysiology; D005704:Gallbladder / Q000737:chemistry / Q000166:cytology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D018408:Patch-Clamp Techniques; D010695:Phlorhizin / Q000494:pharmacology; D011817:Rabbits
D000838:Anions; D000959:Antihypertensive Agents; D001639:Bicarbonates; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D006852:Hydrochlorothiazide; D002245:Carbon Dioxide; D002713:Chlorine; D010695:Phlorhizin