Repolarizing K + Currents I TO1 and I Ks Are Larger in Right Than Left Canine Ventricular Midmyocardium

Abstract

Background—The ventricular action potential exhibits regional heterogeneity in configuration and duration (APD). Across the left ventricular (LV) free wall, this is explained by differences in repolarizing K⁺ currents. However, the ionic basis of electrical nonuniformity in the right ventricle (RV) versus the LV is poorly investigated. We examined transient outward (I_TO1), delayed (I_Ks and I_Kr), and inward rectifier K⁺ currents (I_K1) in relation to action potential characteristics of RV and LV midmyocardial (M) cells of the same adult canine hearts. Methods and Results—Single RV and LV M cells were used for microelectrode recordings and whole-cell voltage clamping. Action potentials showed deeper notches, shorter APDs at 50% and 95% of repolarization, and less prolongation on slowing of the pacing rate in RV than LV. I_TO1 density was significantly larger in RV than LV, whereas steady-state inactivation and rate of recovery were similar. I_Ks tail currents, measured at −25 mV and insensitive to almokalant (2 μmol/L), were considerably larger in RV than LV. I_Kr, measured as almokalant-sensitive tail currents at −50 mV, and I_K1 were not different in the 2 ventricles. Conclusions—Differences in K⁺ currents may well explain the interventricular heterogeneity of action potentials in M layers of the canine heart. These results contribute to a further phenotyping of the ventricular action potential under physiological conditions.