Evaluation of the role of IKAChin atrial fibrillation using a mouse knockout model
Journal of the American College of Cardiology, 2001•jacc.org
OBJECTIVES We sought to study the role of IKAChin atrial fibrillation (AF) and the potential
electrophysiologic effects of a specific IKAChantagonist. BACKGROUND IKAChmediates
much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but
the specific role of IKAChin the generation of AF and the electrophysiologic effects of specific
IKAChblockade have not been studied. METHODS Adult wild-type (WT) and IKACh-deficient
knockout (KO) mice were studied in the absence and presence of the muscarinic receptor …
electrophysiologic effects of a specific IKAChantagonist. BACKGROUND IKAChmediates
much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but
the specific role of IKAChin the generation of AF and the electrophysiologic effects of specific
IKAChblockade have not been studied. METHODS Adult wild-type (WT) and IKACh-deficient
knockout (KO) mice were studied in the absence and presence of the muscarinic receptor …
Abstract
OBJECTIVES
We sought to study the role of IKAChin atrial fibrillation (AF) and the potential electrophysiologic effects of a specific IKAChantagonist.
BACKGROUND
IKAChmediates much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but the specific role of IKAChin the generation of AF and the electrophysiologic effects of specific IKAChblockade have not been studied.
METHODS
Adult wild-type (WT) and IKACh-deficient knockout (KO) mice were studied in the absence and presence of the muscarinic receptor agonist carbachol. The electrophysiologic features of KO mice were compared with those of WT mice to assess the potential effects of a specific IKAChantagonist.
RESULTS
Atrial fibrillation lasting for a mean of 5.7 ± 11 min was initiated in 10 of 14 WT mice in the presence of carbachol, but not in the absence of carbachol. Atrial arrhythmia could not be induced in KO mice. Ventricular tachyarrhythmia could not be induced in either type of mouse. Sinus node recovery times after carbachol and sinus cycle lengths were shorter and ventricular effective refractory periods were greater in KO mice than in WT mice. There was no significant difference between KO and WT mice in AV node function.
CONCLUSIONS
Activation of IKAChpredisposed to AF and lack of IKAChprevented AF. It is likely that IKAChplays a crucial role in the generation of AF in mice. Specific IKAChblockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles.
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