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(Circulation. 2001;103:1585.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Left Ventricular Hypertrophy Decreases Slowly but Not Rapidly Activating Delayed Rectifier Potassium Currents of Epicardial and Endocardial Myocytes in Rabbits

Xiaoping Xu, PhD; Seth J. Rials, MD, PhD; Ying Wu, MD; Joseph J. Salata, PhD; Tengxian Liu, BS; David B. Bharucha, MD, PhD; Roger A. Marinchak, MD; Peter R. Kowey, MD

From Main Line Health Heart Center, Wynnewood, Pa (X.X., Y.W., T.L., D.B.B., R.A.M., P.R.K.); HeartCare, Inc, Columbus, Ohio (S.J.R.); and the Department of Pharmacology, Merck Research Laboratories, West Point, Pa (J.J.S.).

Correspondence to Xiaoping Xu, PhD, Cardiology Foundation of Lankenau, Suite 558, MOB East, 100 Lancaster Ave, Wynnewood, PA 19096. E-mail xxujwang{at}aol.com

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 (I_Ks) and rapidly (I_Kr) 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, 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 similar 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 (40%) in both Epi and Endo but had no significant effect on I_Kr in either Epi or Endo. Consequently, I_Kr was expected to contribute more to AP repolarization in LVH than in control. This was confirmed by specific I_Kr 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 I_Ks blocker) prolonged AP less in LVH than in control. The very small I_Ks 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 I_Ks density and increases the propensity to develop early afterdepolarizations, especially in Endo.

Key Words: action potentials • hypertrophy • ion channels

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