Inactivation properties and frequency-dependence of ultrarapid
delayed rectifier k+ current in human atrial myocytes.
Feng, Jianlin, Donghui Xu, Zhiguo Wang, and Stanley_nattel,.
Department of 1Medicine and 2Research Center, Montreal Heart
Institute, Montreal H1T 1C8; Department of 3Medicine, University of
Montreal, Montreal H3C 3J7; and the Department of 4Pharmacology and
Therapeutics, McGill University, Montreal H3G 1Y6, Quebec, Canada
APStracts 5:0310H, 1998.
The ultrarapid delayed rectifier current (IKur) plays a significant
role in human atrial repolarization and is generally believed to show
little rate-dependence because of slow and partial inactivation. This
study was designed to evaluate in detail the properties and
consequences of IKur inactivation in isolated human atrial myocytes.
IKur inactivated with a biexponential time course and a half
-inactivation voltage of -7.5 " 0.6 mV (mean " SE), with
complete inactivation during 50-s pulses to voltages positive to +10
mV (37_C). Recovery from inactivation proceeded slowly, with time
constants of 0.42 " 0.06 and 7.9 " 0.9 s at -80 mV.
Substantial frequencydependence was observed at 37_C over a
clinically-relevant range of frequencies. Inactivation was faster and
occurred at more positive voltages at 37_C compared to room
temperature. The voltageand timedependencies of Kv1.5 inactivation
were studied in Xenopus oocytes to avoid overlapping currents, and
strongly resembled those of IKur in native myocytes. We conclude
that, while IKur inactivation is slow, it is extensive, and slow
recovery from inactivation confers important frequency-dependence
with significant consequences for understanding the role of IKur in
human atrial repolarization.
Received 9 April 1998; accepted in final form 20 July 1998.
APS Manuscript Number H279-8.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998