A novel anionic conductance affects action potential duration in isolated rat ventricular myocytes

Effects of extracellular anions were studied in electrophysiological experi ments on freshly isolated rat ventricular myocytes. Under current-clamp, ac tion potential duration (APD) was prolonged by reducing the extracellular C l- concentration and shortened by replacement of extracellular Cl- with I-. Under voltage-clamp, membrane potential steps or ramps evoked an anionic b ackground current (I-AB) carried by either Cl-, Br-, I- or NO3-. Activation of I-AB was Ca2+- and cyclic AMP-independent, and was unaffected by cell s hrinkage. I-AB was insensitive to stilbene and fenamate anion transport blo ckers at concentrations that inhibit Ca2+ -, cyclic AMP- and swelling-activ ated Cl- currents in ventricular cells of other mammals. These results sugg est that I-AB may be carried by a novel class of Cl- channel. Correlation o f anion substitution experiments on membrane current and action potentials revealed that IAB could play a major role in controlling rat ventricular AP D. These findings have important implications for those studying cardiac Cl - channels as potential targets for novel antiarrythmic agents.