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. British Journal of Pharmacology (2000) 129 , 235–238; doi: 10.1038/sj.bjp.0703074