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Atrial tachycardia induces remodelling of muscarinic receptors and their coupled potassium currents in canine left atrial and pulmonary vein cardiomyocytes.
Br J Pharmacol. 2007 Dec; 152(7):1021-32.BJ

Abstract

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 (M2, M3, M4) in atrial cardiomyocytes are coupled to distinct K+-currents (called IKM2, IKM3, IKM4, 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. IKM2, IKM3 and IKM4 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 IKM2, IKM3 and IKM4 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 M2, M3 and M4 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.

Authors+Show Affiliations

Department of Medicine, Université de Montréal and Research Center, Montreal Heart Institute, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17618308

Citation

Yeh, Y-H, et al. "Atrial Tachycardia Induces Remodelling of Muscarinic Receptors and Their Coupled Potassium Currents in Canine Left Atrial and Pulmonary Vein Cardiomyocytes." British Journal of Pharmacology, vol. 152, no. 7, 2007, pp. 1021-32.
Yeh YH, Qi X, Shiroshita-Takeshita A, et al. Atrial tachycardia induces remodelling of muscarinic receptors and their coupled potassium currents in canine left atrial and pulmonary vein cardiomyocytes. Br J Pharmacol. 2007;152(7):1021-32.
Yeh, Y. H., Qi, X., Shiroshita-Takeshita, A., Liu, J., Maguy, A., Chartier, D., Hebert, T., Wang, Z., & Nattel, S. (2007). Atrial tachycardia induces remodelling of muscarinic receptors and their coupled potassium currents in canine left atrial and pulmonary vein cardiomyocytes. British Journal of Pharmacology, 152(7), 1021-32.
Yeh YH, et al. Atrial Tachycardia Induces Remodelling of Muscarinic Receptors and Their Coupled Potassium Currents in Canine Left Atrial and Pulmonary Vein Cardiomyocytes. Br J Pharmacol. 2007;152(7):1021-32. PubMed PMID: 17618308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atrial tachycardia induces remodelling of muscarinic receptors and their coupled potassium currents in canine left atrial and pulmonary vein cardiomyocytes. AU - Yeh,Y-H, AU - Qi,X, AU - Shiroshita-Takeshita,A, AU - Liu,J, AU - Maguy,A, AU - Chartier,D, AU - Hebert,T, AU - Wang,Z, AU - Nattel,S, Y1 - 2007/07/09/ PY - 2007/7/10/pubmed PY - 2008/2/6/medline PY - 2007/7/10/entrez SP - 1021 EP - 32 JF - British journal of pharmacology JO - Br J Pharmacol VL - 152 IS - 7 N2 - 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 (M2, M3, M4) in atrial cardiomyocytes are coupled to distinct K+-currents (called IKM2, IKM3, IKM4, 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. IKM2, IKM3 and IKM4 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 IKM2, IKM3 and IKM4 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 M2, M3 and M4 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17618308/Atrial_tachycardia_induces_remodelling_of_muscarinic_receptors_and_their_coupled_potassium_currents_in_canine_left_atrial_and_pulmonary_vein_cardiomyocytes_ L2 - https://doi.org/10.1038/sj.bjp.0707376 DB - PRIME DP - Unbound Medicine ER -