Ik of rabbit ventricle is composed of two currents: evidence for
the slowly activating current iks.
Salata, Joseph J., Nancy K. Jurkiewicz, Brian Jow, Kimberly Folander,
Peter J. Guinosso, Jr., Bryan Raynor, Richard Swanson, and Bernard
Fermini.
Department of Pharmacology, Merck Research Laboratories, West
Point, PA 19486
APStracts 3:0211H, 1996.
The delayed rectifier K+ current (IK) in rabbit heart has long been
thought to consist of only a single, rapidly-activating, dofetilide
-sensitive current, IKr. However, we find that IK of rabbit
ventricular myocytes actually consists of both rapid and slow
components, IKr and IKs, that can be isolated pharmacologically.
Thus, after complete blockade of IKr with dofetilide, the remaining
current, IKs, is homogeneous as judged by an envelope of tails test.
IKs activates and deactivates slowly, continues to activate during
sustained depolarizations, has a half-activation potential of 7.0+/
-0.8 mV and slope factor of 11.0+/-0.7 mV, reverses at -77.2+/-1.3 mV
([K+]e = 4 mM), is increased by removing K+e, and is enhanced by
isoproterenol and blocked by azimilide. Northern analysis
demonstrates that the IsK (or minK) gene, which encodes a subunit of
the channel that underlies the IKs current, is expressed in rabbit
heart. Expression of the rabbit protein in Xenopus oocytes elicits a
slowly activating, voltage-dependent current, IsK, similar to those
expressed previously from mouse, rat, guinea pig and human genes. The
results demonstrate that IKs is present in rabbit ventricle and may,
therefore, contribute to cardiac repolarization in this species.
Received 22 January 1996; accepted in final form 23 April 1996.
APS Manuscript Number H52-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96