| First Author | Pahlavan S | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 95 |
| Issue | 1 | Pages | 48-58 |
| PubMed ID | 22562663 | Mgi Jnum | J:202575 |
| Mgi Id | MGI:5520032 | Doi | 10.1093/cvr/cvs162 |
| Citation | Pahlavan S, et al. (2012) Galphaq and Galpha11 contribute to the maintenance of cellular electrophysiology and Ca2+ handling in ventricular cardiomyocytes. Cardiovasc Res 95(1):48-58 |
| abstractText | AIMS: Galpha(q) and Galpha(11) signalling pathways contribute to cardiac diseases such as hypertrophy and arrhythmia, but their role in cardiac myocytes from healthy hearts has remained unclear. We aimed to investigate the contribution of Galpha(q) and Galpha(11) signalling to the basal properties of ventricular myocytes. METHODS AND RESULTS: We created a conditional Galpha(q) knockout (KO) after tamoxifen injection into gnaq(flox/flox) gna11(-/-) alpha-MHC Cre(tg/0) mice and found alterations in the electrophysiological and Ca(2+) handling properties of ventricular myocytes using patch-clamp and Fura-2 video imaging. To reveal the genuine effects of protein KO, we investigated the individual contributions of (i) tamoxifen injection, (ii) Cre recombinase expression, (iii) Galpha(11) KO, and (iv) Galpha(q) KO. Profound and persistent alterations in myocyte properties occurred following the tamoxifen injection alone. Consequently, we used the presence or absence of Cre recombinase expression as the determinant for the Galpha(q) KO. Myocytes from the Galpha(q) and/or Galpha(11) KO mice displayed genuine alterations in the action potentials, membrane capacitance, membrane currents, and Ca(2+) handling (amplitude, post-rest behaviour, and Ca(2+) removal processes). CONCLUSIONS: We conclude that, in a transgenic model, the role of Galpha(q) can be best studied using Cre recombinase expression as the molecular determinant for Galpha(q) KO rather than tamoxifen/miglyol injection. While excessive hormonal stimulation of the Galpha(q)/Galpha(11) signalling pathways plays an essential role in cardiac diseases, we propose that the persistent low-level stimulation of these pathways by Galpha(q)/Galpha(11) activation is instrumental in the physiological behaviour of ventricular myocytes. |
