Channelpedia

PubMed 21546445


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Slo1 , TRP , TRPC , TRPC6



Title: Regulation of murine cardiac contractility by activation of α(1A)-adrenergic receptor-operated Ca(2+) entry.

Authors: Marion C Mohl, Siiri E Iismaa, Xiao-Hui Xiao, Oliver Friedrich, Soeren Wagner, Vesna Nikolova-Krstevski, Jianxin Wu, Ze-Yan Yu, Michael Feneley, Diane Fatkin, David G Allen, Robert M Graham

Journal, date & volume: Cardiovasc. Res., 2011 Jul 15 , 91, 310-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21546445


Abstract
Sympathetic 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.Using 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.These 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.