Different intracellular polyamine concentrations underlie the difference in the inward rectifier K+ currents in atria and ventricles of the guinea-pig heart

Abstract

The outward component of the strong inward rectifier potassium current, IK1, is significantly larger in ventricles than in atria of the heart, resulting in faster repolarization at the final phase of the action potential in ventricles. However, the underlying mechanism of the difference in IK1 remains poorly understood. IK1 channels are composed of subunits from the Kir2 subfamily, and IK1 amplitude is determined by the voltage-dependent blockade of the channel by the intracellular polyamines spermine and spermidine, and by Mg2+. Using a perforated patch-clamp method, which minimizes changes in the intracellular polyamine and Mg2+ concentrations, we detected repolarization-induced outward IK1 transients, which are caused by competition between Mg2+ and spermine to block the channel, in ventricular but not in atrial myocytes from guinea-pig heart. The contribution of the Kir2.3 subunit to the IK1 channel was found to be minor in the guinea-pig heart, because the activation time course of the Kir2.3 currents was ∼10-fold slower than those of IK1, and the marked external pH sensitivity of the Kir2.3 currents was not found in IK1. Both the Kir2.1 and Kir2.2 currents recorded from inside-out patches exhibited outward transients similar to those of ventricular IK1 in the presence of 5-10 μM spermine and 0.6-1.1 μM Mg2+, and their amplitudes were diminished by increasing the spermine or spermidine concentrations. The total and free polyamine concentrations in guinea-pig cardiac tissues were higher in atria than ventricles. These results strongly suggest that different intracellular polyamine concentrations are responsible for the difference in atrial and ventricular IK1 of the guinea-pig heart. © The Physiological Society 2005.