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

Background-Delayed rectifier K+ currents are critical to action potential ( AP) repolarization. The present study examines the effects of left ventricu lar hypertrophy (LVH) on delayed rectifier K+ currents and their contributi on to AP repolarization in both epicardial (Epi) and endocardial (Endo) myo cytes. Methods and Results-LVH was induced in rabbits by a I-kidney removal, 1-kid ney vascular clamping method. Slowly (I-Ks) and rapidly (I-Kr) activating d elayed rectifier K+ currents were recorded by the whole-cell patch-clamp te chnique, and APs were recorded by the microelectrode technique. In normal r abbit left ventricular myocytes, I-Ks densities were larger in Epi than in Endo (1.1 +/-0.1 versus 0.43 +/-0.07 pA/pF), whereas I-Kr density was simil ar between Epi and Endo (0.31 +/-0.05 versus 0.36 +/-0.07 pA/pF) at 20 mV. LVH reduced I-Ks density to a similar extent (approximate to 40%) in both E pi and Endo but had no significant effect on I-Kr in either Epi or Endo. Co nsequently, I-Kr was expected to contribute more to AP repolarization in LV H than in control. This was confirmed by specific I-Kr block with dofetilid e, which prolonged AP significantly more in LVH than in control (31 +/-3% v ersus 18 +/-2% in Epi; 53 +/-6% versus 32 +/-4% in Endo at 2 Hz). In contra st, L-768,673 (a specific I-Ks blocker) prolonged AP less in LVH than in co ntrol. The very small I-Ks density in Endo with LVH is consistent with the greater incidence of early afterdepolarizations induced in this region by d ofetilide. Conclusions-LVH induces a decrease in I-Ks density and increases the propen sity to develop early afterdepolarizations, especially in Endo.