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 ventricular hypertrophy (LVH) on delayed rectifier K(+) currents and their contribution to AP repolarization in both epicardial (Epi) and endocardial (Endo) myocytes.


RESULTS
VH 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 (approximately 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.
Xu
X
X
Main Line Health Heart Center, Wynnewood, PA, USA. xxujwang@aol.com
Rials
S J
SJ
Wu
Y
Y
Salata
J J
JJ
Liu
T
T
Bharucha
D B
DB
Marinchak
R A
RA
Kowey
P R
PR
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D004594:Electrophysiology; D004699:Endocardium / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010496:Pericardium / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011817:Rabbits
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated