Left ventricular hypertrophy decreases slowly but not rapidly activating delayed rectifier potassium currents of epicardial and endocardial myocytes in rabbits

Abstract

Background - Delayed rectifier K+ currents are critical to action potential (AP) repolarization. The present study examines the effects of left ventricular hypertrophy (LVH) on delayed rectifier K+ currents and their contribution to AP repolarization in both epicardial (Epi) and endocardial (Endo) myocytes. Methods and Results - LVH was induced in rabbits by a 1-kidney removal, 1-kidney vascular clamping method. Slowly (IKs) and rapidly (IKr) activating delayed rectifier K+ currents were recorded by the whole-cell patch-clamp technique, and APs were recorded by the microelectrode technique. In normal rabbit left ventricular myocytes, IKs densities were larger in Epi than in Endo (1.1 ± 0.1 versus 0.43 ± 0.07 pA/pF), whereas IKr density was similar between Epi and Endo (0.31±0.05 versus 0.36 ± 0.07 pA/pF) at 20 mV. LVH reduced IKs density to a similar extent (≈40%) in both Epi and Endo but had no significant effect on IKr in either Epi or Endo. Consequently, IKr was expected to contribute more to AP repolarization in LVH than in control. This was confirmed by specific IKr block with dofetilide, which prolonged AP significantly more in LVH than in control (31 ± 3% versus 18±2% in Epi; 53±6% versus 32±4% in Endo at 2 Hz). In contrast, L-768,673 (a specific IKs blocker) prolonged AP less in LVH than in control. The very small IKs density in Endo with LVH is consistent with the greater incidence of early afterdepolarizations induced in this region by dofetilide. Conclusions - LVH induces a decrease in IKs density and increases the propensity to develop early afterdepolarizations, especially in Endo.