(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
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
(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.
Key Words: action potentials • hypertrophy • ion channels
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