Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions

Abstract

The mechanism of rectification of the inwardly rectifying potassium channel was examined with single-channel recording techniques in isolated ventricular myocytes from adult guinea pig heart. Inward, or anomalous, rectification describes the property that potassium (K) current can enter the cell at potentials negative to the potassium equilibrium potential, E(K), more readily than it can leave the cell at positive potentials. Voltage ramps applied to single inward rectifier channels in cell-attached patches produced single-channel currents that rectified strongly with a marked reduction in current at a potential near E(K). At more positive potentials no current could be detected. Rectification was influenced by external and internal K concentrations. Single-channel activity, which usually disappears rapidly in excised patches, could be maintained by removing calcium from the internal solution. Rectification could be eliminated by excision of the patch into an internal solution in which free magnesium (Mg2+) was reduced to < 1 μM, and it could be restored by the addition of ~ mM Mg2+ to the internal solution. At intermediate concentrations of Mg2+, intermediate degrees of rectification were obtained, and the current at potentials positive to E(K) was often interrupted by brief closures. These studies suggest that rectification is due to internal block by Mg2+, possibly the results of rapid block of the open channel.