Reducing extracellular Cl(-) concentration prolonged action potential duration, while replacing Cl(-) with I(-) shortened it, revealing a novel anionic background current in rat ventricular myocytes.
Does altering extracellular anions affect action potential duration in isolated rat ventricular myocytes?
A novel anionic background current plays a major role in controlling rat ventricular action potential duration, suggesting a potential target for novel antiarrhythmic agents.
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 et al. (2000) studied this question. Extracellular anion substitution vs. Normal extracellular Cl(-) concentration was evaluated on Action potential duration (APD) and anionic background current (I(AB)). Reducing extracellular Cl(-) concentration prolonged action potential duration, while replacing Cl(-) with I(-) shortened it, revealing a novel anionic background current in rat ventricular myocytes.