Repolarizing K ⁺ Currents <i>I</i> _TO1 and <i>I</i> _Ks Are Larger in Right Than Left Canine Ventricular Midmyocardium

TLDR

The canine ventricular action potential shows regional heterogeneity, largely attributed to differences in repolarizing K⁺ currents, yet the ionic basis of right‑ventricular versus left‑ventricular nonuniformity remains poorly understood. We performed microelectrode recordings and whole‑cell voltage clamping on single midmyocardial cells from the right and left ventricles of adult canine hearts to measure I_TO1, I_Ks, I_Kr, and I_K1 currents. Right‑ventricular cells exhibited deeper notches, shorter APDs, and less rate‑dependent prolongation, with significantly larger I_TO1 and I_Ks tail currents compared to left‑ventricular cells, while I_Kr and I_K1 were unchanged, indicating that K⁺ current differences underlie interventricular action‑potential heterogeneity.

Abstract

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 (ITO1), delayed (IKs and IKr), and inward rectifier K+ currents (IK1) in relation to action potential characteristics of RV and LV midmyocardial (M) cells of the same adult canine hearts.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. ITO1 density was significantly larger in RV than LV, whereas steady-state inactivation and rate of recovery were similar. IKs tail currents, measured at -25 mV and insensitive to almokalant (2 micromol/L), were considerably larger in RV than LV. IKr, measured as almokalant-sensitive tail currents at -50 mV, and IK1 were not different in the 2 ventricles.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.