Affiliation:
1. From the Department of Pharmacology and Toxicology, (D.D., E.G., E.W., H.M.H., O.H., C.D., T.C., U.R.) and Cardiovascular Centre Dresden (S.S.), Medical Faculty, University of Technology, Dresden, Germany.
Abstract
Background
Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K
+
current (
I
K,ACh
) contribute to chronic AF.
Methods and Results
In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in
I
K,ACh
and the level of the
I
K,ACh
GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of
I
K,ACh
was ≈50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K
+
current (
I
K1
) was 2-fold larger during AF than in sinus rhythm, in correspondence with an increase in Kir2.1 mRNA. The larger
I
K1
in AF is consistent with more negative membrane potentials in right atrial trabeculae from AF patients. Moreover, action potential duration was reduced in AF, and the action potential shortening produced by muscarinic receptor stimulation was attenuated, indicating that the changes of
I
K1
and
I
K,ACh
were functionally relevant.
Conclusions
Chronic human AF induces transcriptionally mediated upregulation of
I
K1
but downregulation of
I
K,ACh
and attenuates the muscarinic receptor–mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating
I
K,ACh
to counteract the shortening of the atrial effective refractory period due to electrical remodeling.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Reference26 articles.
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2. Role of atrial electrophysiology and autonomic nervous system in patients with supraventricular tachycardia and paroxysmal atrial fibrillation
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