1. Left Ventricular Hypertrophy Decreases Slowly but Not Rapidly Activating Delayed Rectifier Potassium Currents of Epicardial and Endocardial Myocytes in Rabbits
- Author
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Ying Wu, David B. Bharucha, Xiaoping Xu, Peter R. Kowey, Joseph J. Salata, Seth J. Rials, Tengxian Liu, and Roger A. Marinchak
- Subjects
Male ,medicine.medical_specialty ,Potassium Channels ,Action Potentials ,Left ventricular hypertrophy ,Muscle hypertrophy ,Physiology (medical) ,Internal medicine ,Animals ,Medicine ,Repolarization ,Myocyte ,Ion channel ,Endocardium ,Lagomorpha ,biology ,business.industry ,Myocardium ,biology.organism_classification ,medicine.disease ,Electrophysiology ,Endocrinology ,Potassium Channels, Voltage-Gated ,Cardiology ,Hypertrophy, Left Ventricular ,Rabbits ,Cardiology and Cardiovascular Medicine ,business ,Pericardium ,Delayed Rectifier Potassium Channels - 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 ( 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.
- Published
- 2001