Heterogeneous expression of repolarizing, voltage-gated K+ currents in adult mouse ventricles

Previous studies have documented the expression of four kinetically distinct voltage-gated K+ (Kv) currents, I-to,I-f, I-to,I-s, I-K,I-slow and I-ss, in mouse ventricular myocytes and demonstrated that I-to,I-f and I-to,I-s are differentially expressed in the left ventricular apex and the interventricular septum. The experiments here were undertaken to test the hypothesis that there are further regional differences in the expression of Kv currents or the Kv subunits (Kv4.2, Kv4.3, KChIP2, Kv1.5, Kv2.1) encoding these currents in adult male and female (C57BL6) mouse ventricles. Whole-cell voltage-clamp recordings revealed that mean (+/- S.E.M.) peak outward K+ current and Ito,f densities are significantly (P < 0.001) higher in cells isolated from the right (RV) than the left (LV) ventricles. Within the LV, peak outward K+ current and I-to,I-f densities are significantly (P < 0.05) higher in cells from the apex than the base. In addition, I-to,I-f and I-K,I-slow densities are lower in cells isolated from the endocardial (Endo) than the epicardial (Epi) surface of the LV wall. Importantly, similar to LV apex cells, I-to,I-s is not detected in RV, LV base, LV Epi or LV Endo myocytes. No measurable differences in K+ current densities or properties are evident in RV or LV cells from adult male and female mice, although I-to,I-f, I-to,I-s, I-K,I-slow and I-ss densities are significantly (P <0.01) higher, and action potential durations at 50% (APD(50)) are significantly (P < 0.05) shorter in male septum cells. Western blot analysis revealed that the expression levels of Kv4.2, Kv4.3, KChIP2, Kv1.5 and Kv2.1 are similar in male and female ventricles. In addition, consistent with the similarities in repolarizing Kv current densities, no measurable differences in ECG parameters, including corrected QT (QT(c)) intervals, are detected in telemetric recordings from adult male and female (C57BL6) mice.