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Atrial tachycardia induces remodelling of muscarinic receptors and their coupled potassium currents in canine left atrial and pulmonary vein cardiomyocytes
Author(s) -
Yeh YH,
Qi X,
ShiroshitaTakeshita A,
Liu J,
Maguy A,
Chartier D,
Hebert T,
Wang Z,
Nattel S
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707376
Subject(s) - muscarinic acetylcholine receptor , medicine , atrial fibrillation , muscarinic acetylcholine receptor m2 , potassium channel , cholinergic , endocrinology , agonist , patch clamp , cardiology , pulmonary vein , receptor , chemistry
Background and purpose: Both parasympathetic tone and atrial tachycardia (AT) remodelling of ion channels play important roles in atrial fibrillation (AF) pathophysiology. Different muscarinic cholinergic receptor (mAChR) subtypes (M 2 , M 3 , M 4 ) in atrial cardiomyocytes are coupled to distinct K + ‐currents (called I KM2 , I KM3 , I KM4 , respectively). Pulmonary veins (PVs) are important in AF and differential cholinergic current responses are a potential underlying mechanism. This study investigated AT‐induced remodelling of mAChR subtypes and K + ‐currents in left‐atrial (LA) and PV cardiomyocytes. Experimental approach: Receptor expression was assayed by western blot. I KM2 , I KM3 and I KM4 were recorded with whole‐cell patch‐clamp in LA and PV cardiomyocytes of nonpaced control dogs and dogs after 7 days of AT‐pacing (400 bpm). Key results: Current densities of I KM2 , I KM3 and I KM4 were significantly reduced by AT‐pacing in LA and PV cardiomyocytes. PV cardiomyocyte current–voltage relations were similar to LA for all three cholinergic currents, both in control and AT remodelling. Membrane‐protein expression levels corresponding to M 2 , M 3 and M 4 subtypes were decreased significantly (by about 50%) after AT pacing. Agonist concentration–response relations for all three currents were unaffected by AT pacing. Conclusions and implications: AT downregulated all three mAChR‐coupled K + ‐current subtypes, along with corresponding mAChR protein expression. These changes in cholinergic receptor‐coupled function may play a role in AF pathophysiology. Cholinergic receptor‐coupled K + ‐currents in PV cardiomyocytes were similar to those in LA under control and AT‐pacing conditions, suggesting that differential cholinergic current properties do not explain the role of PVs in AF. British Journal of Pharmacology (2007) 152 , 1021–1032; doi: 10.1038/sj.bjp.0707376 ; published online 9 July 2007