© 1997 American Heart Association, Inc.
Articles |
Outward K+ Current Densities and Kv1.5 Expression Are Reduced in Chronic Human Atrial Fibrillation
From the Departments of Cardiology (D.R. Van W.) and Cardiothoracic Surgery (P.M.M.), The Cleveland (Ohio) Clinic Foundation; the Department of Molecular Biology and Pharmacology (A.L.P., J.M.N.), Washington University School of Medicine, St Louis, Mo; and the Department of Biochemistry and Cell Biology (J.S.T.), State University of New York at Stony Brook.
Correspondence to Jeanne M. Nerbonne, PhD, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110. E-mail jnerbonn{at}pharmdec.wustl.edu
Abstract Chronic atrial fibrillation is associated with a
shortening of the atrial action potential duration and atrial
refractory period. To test the hypothesis that these changes are
mediated by changes in the density of specific atrial K+
currents, we compared the density of K+ currents in left
and right atrial myocytes and the density of delayed rectifier
K+ channel 
-subunit proteins (Kv1.5 and Kv2.1) in left
and right atrial appendages from patients (n=28) in normal sinus rhythm
with those from patients (n=15) in chronic atrial fibrillation (AF).
Contrary to our expectations, nystatin–perforated patch
recordings of whole-cell K+ currents revealed
significant reductions in both the inactivating
(ITO) and sustained
(IKsus) outward K+ current densities
in left and right atrial myocytes isolated from patients in chronic AF,
relative to the ITO and
IKsus densities in myocytes isolated from
patients in normal sinus rhythm. Quantitative Western blot
analysis revealed that although there was no change in the
expression of the Kv2.1 protein, the expression of Kv1.5 protein was
reduced by >50% in both the left and the right atrial appendages of
AF patients. The finding that Kv1.5 expression is reduced in parallel
with the reduction in delayed rectifier K+ current density
is consistent with recent suggestions that Kv1.5 underlies the
major component of the delayed rectifier K+ current in
human atrial myocytes, the ultrarapid delayed rectifier K+
current, IKur. The unexpected finding of reduced
voltage-gated outward K+ current densities in atrial
myocytes from AF patients demonstrates the need to further examine the
details of the electrophysiological
remodeling that occurs during AF to enable more effective and safer
therapeutic strategies to be developed.
Key Words: K+ channels • atrial fibrillation • Kv1.5 • Kv2.1 • action potential duration
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