More types than one: multiple muscarinic receptor coupled K+ currents undergo remodelling in an experimental model of atrial fibrillation.
The common cardiac arrhythmia atrial fibrillation (AF) tends to show progression in its severity, which is associated with 'remodelling': structural and electrophysiological changes that facilitate arrhythmia induction and maintenance. In this issue of the BJP, Yeh and colleagues demonstrate for the first time, down-regulation of three types of muscarinic cholinergic receptor (mAChR) coupled K+ currents (IKM2, IKM3 and IKM4) and of M2, M3 and M4 mAChR subtype proteins, in a canine model of atrial tachycardia (AT) induced remodelling. The IKMs and their extent of AT-induced remodelling were similar in left-atrial and pulmonary vein (PV) myocytes, so remodelling of M2-M4 receptor-linked currents appears not to underlie the unique contribution of PVs to AF. Parasympathetic stimulation can increase susceptibility to AF; thus remodelling of M2-M4 receptors and K+ currents could be adaptive in AT. Further work is warranted to determine whether or not remodelling of multiple mAChRs and currents also contributes to human AF.
James
A F
AF
Department of Physiology and Pharmacology, and Bristol Heart Institute Cardiovascular Research Laboratories, School of Medical Sciences, University of Bristol, Bristol, UK. a.james@bristol.ac.uk
Hancox
J C
JC
D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013612:Tachycardia, Ectopic Atrial / Q000378:metabolism / Q000503:physiopathology