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
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
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.
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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