Regulation of murine cardiac contractility by activation of α(1A)-adrenergic receptor-operated Ca(2+) entry.
Mohl MC, Iismaa SE, Xiao XH, Friedrich O, Wagner S, Nikolova-Krstevski V, Wu J, Yu ZY, Feneley M, Fatkin D, Allen DG, Graham RM (2011)
Publication Language: English
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2011
Journal
Book Volume: 91
Pages Range: 310-9
Journal Issue: 2
URI: http://cardiovascres.oxfordjournals.org/content/cardiovascres/91/2/310.full.pdf
DOI: 10.1093/cvr/cvr081
Open Access Link: http://cardiovascres.oxfordjournals.org/content/cardiovascres/91/2/310.full.pdf
Abstract
AIMS\nSympathetic regulation of cardiac contractility is mediated in part by α(1)-adrenergic receptors (ARs), and the α(1A)-subtype has been implicated in the pathogenesis of cardiac hypertrophy. However, little is known about α(1A)-AR signalling pathways in ventricular myocardium. The aim of this study was to determine the signalling pathway that mediates α(1A)-AR-coupled cardiac contractility.\nMETHODS AND RESULTS\nUsing a transgenic model of enhanced cardiac α(1A)-AR expression and signalling (α(1A)-H mice), we identified a receptor-coupled signalling pathway that enhances Ca(2+) entry and increases contractility. This pathway involves α(1A)-AR-activated translocation of Snapin and the transient receptor potential canonical 6 (TRPC6) channel to the plasma membrane. In ventricular cardiomyocytes from α(1A)-H and their non-transgenic littermates (or WTs), stimulation with α(1A)-AR-specific agonists resulted in increased [Ca(2+)](i), which was dose-related and proportional to the level of α(1A)-AR expression. Blockade of TRPC6 inhibited the α(1A)-AR-mediated increase in [Ca(2+)](i) and contractility. External Ca(2+) entry, underlying the [Ca(2+)](i) increase, was not due to store-operated Ca(2+) entry but to a receptor-operated mechanism of Ca(2+) entry resulting from α(1A)-AR activation.\nCONCLUSION\nThese findings indicate that Ca(2+) entry via the α(1A)-AR-Snapin-TRPC6-pathway plays an important role in physiological regulation of cardiac contractility and may be an important target for augmenting cardiac performance.
Authors with CRIS profile
Oliver Friedrich
Lehrstuhl für Medizinische Biotechnologie
Sören Wagner
Department of Anaesthesiology
Involved external institutions
Australia (AU)How to cite
APA:
Mohl, M.C., Iismaa, S.E., Xiao, X.-H., Friedrich, O., Wagner, S., Nikolova-Krstevski, V.,... Graham, R.M. (2011). Regulation of murine cardiac contractility by activation of α(1A)-adrenergic receptor-operated Ca(2+) entry. Cardiovascular Research, 91(2), 310-9. https://doi.org/10.1093/cvr/cvr081
MLA:
Mohl, Marion C., et al. "Regulation of murine cardiac contractility by activation of α(1A)-adrenergic receptor-operated Ca(2+) entry." Cardiovascular Research 91.2 (2011): 310-9.
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