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(Circulation. 2000;101:2631.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology
From the Department of Medicine, Montreal Heart Institute and University of Montreal (D.L., J.F., Z.W., S.N.), and the Departments of Pharmacology (S.N.), Physiology (K.P., A.S.), and Pathology (P.M.), McGill University, Montreal, Quebec, Canada.
Correspondence to Dr Stanley Nattel, Research Center, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec, Canada, H1T 1C8. E-mail nattel{at}icm.umontreal.ca
Background—Congestive heart failure (CHF) is frequently associated with atrial fibrillation (AF), but little is known about the effects of CHF on atrial cellular electrophysiology.
Methods and Results—We studied action potential (AP) properties
and ionic currents in atrial myocytes from dogs with CHF induced by
ventricular pacing at 220 to 240 bpm for 5 weeks. Atrial
myocytes from CHF dogs were hypertrophied (mean±SEM capacitance, 89±2
pF versus 71±2 pF in control, n=160 cells per group,
P<0.001). CHF significantly reduced the density of
L-type Ca2+ current (ICa) by
30%, of transient outward K+ current
(Ito) by 50%, and of slow delayed
rectifier current (IKs) by 30% without
altering their voltage dependencies or kinetics. The inward rectifier,
ultrarapid and rapid delayed rectifier, and T-type Ca2+
currents were not altered by CHF. CHF increased transient inward
Na+/Ca2+ exchanger (NCX) current by 45%.
The AP duration of atrial myocytes was not altered by CHF at slow rates
but was increased at faster rates, paralleling in vivo refractory
changes. CHF created a substrate for AF, prolonging mean AF duration
from 8±4 to 535±82 seconds (P<0.01).
Conclusions—Experimental CHF selectively decreases atrial Ito, ICa, and IKs, increases NCX current, and leaves other currents unchanged. The cellular electrophysiological remodeling caused by CHF is quite distinct from that caused by atrial tachycardia, highlighting important differences in the cellular milieu characterizing different clinically relevant AF substrates.
Key Words: ion channels • biophysics • electrophysiology
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