A novel anionic conductance affects action potential duration in isolated rat ventricular myocytes.
Effects of extracellular anions were studied in electrophysiological experiments on freshly isolated rat ventricular myocytes. Under current-clamp, action potential duration (APD) was prolonged by reducing the extracellular Cl(-) concentration and shortened by replacement of extracellular Cl(-) with I(-). Under voltage-clamp, membrane potential steps or ramps evoked an anionic background current (I(AB)) carried by either Cl(-), Br(-), I(-) or NO(3)(-). Activation of I(AB) was Ca(2+)- and cyclic AMP-independent, and was unaffected by cell shrinkage. I(AB) was insensitive to stilbene and fenamate anion transport blockers at concentrations that inhibit Ca(2+)-, cyclic AMP- and swelling-activated Cl(-) currents in ventricular cells of other mammals. These results suggest that I(AB) may be carried by a novel class of Cl(-) channel. Correlation of anion substitution experiments on membrane current and action potentials revealed that I(AB) could play a major role in controlling rat ventricular APD. These findings have important implications for those studying cardiac Cl(-) channels as potential targets for novel antiarrythmic agents.
Spencer
C I
CI
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, U.K.
Uchida
W
W
Kozlowski
R Z
RZ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D016276:Ventricular Function
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018118:Chloride Channels; D009544:Niflumic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium