| First Author | Mohl MC | Year | 2011 |
| Journal | Cardiovasc Res | Volume | 91 |
| Issue | 2 | Pages | 310-9 |
| PubMed ID | 21546445 | Mgi Jnum | J:191627 |
| Mgi Id | MGI:5462178 | Doi | 10.1093/cvr/cvr081 |
| Citation | Mohl MC, et al. (2011) Regulation of murine cardiac contractility by activation of alpha(1A)-adrenergic receptor-operated Ca(2+) entry. Cardiovasc Res 91(2):310-9 |
| abstractText | AIMS: Sympathetic regulation of cardiac contractility is mediated in part by alpha(1)-adrenergic receptors (ARs), and the alpha(1A)-subtype has been implicated in the pathogenesis of cardiac hypertrophy. However, little is known about alpha(1A)-AR signalling pathways in ventricular myocardium. The aim of this study was to determine the signalling pathway that mediates alpha(1A)-AR-coupled cardiac contractility. METHODS AND RESULTS: Using a transgenic model of enhanced cardiac alpha(1A)-AR expression and signalling (alpha(1A)-H mice), we identified a receptor-coupled signalling pathway that enhances Ca(2+) entry and increases contractility. This pathway involves alpha(1A)-AR-activated translocation of Snapin and the transient receptor potential canonical 6 (TRPC6) channel to the plasma membrane. In ventricular cardiomyocytes from alpha(1A)-H and their non-transgenic littermates (or WTs), stimulation with alpha(1A)-AR-specific agonists resulted in increased [Ca(2+)](i), which was dose-related and proportional to the level of alpha(1A)-AR expression. Blockade of TRPC6 inhibited the alpha(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 alpha(1A)-AR activation. CONCLUSION: These findings indicate that Ca(2+) entry via the alpha(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. |
