| First Author | Yamakawa H | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 452 |
| Issue | 3 | Pages | 701-7 |
| PubMed ID | 25193703 | Mgi Jnum | J:319089 |
| Mgi Id | MGI:6862675 | Doi | 10.1016/j.bbrc.2014.08.126 |
| Citation | Yamakawa H, et al. (2014) Suppression of Rad leads to arrhythmogenesis via PKA-mediated phosphorylation of ryanodine receptor activity in the heart. Biochem Biophys Res Commun 452(3):701-7 |
| abstractText | Ras-related small G-protein Rad plays a critical role in generating arrhythmias via regulation of the L-type Ca(2+) channel (LTCC). The aim was to demonstrate the role of Rad in intracellular calcium homeostasis by cardiac-Specific dominant-negative suppression of Rad. Transgenic (TG) mice overexpressing dominant-negative mutant Rad (S105N Rad TG) were generated. To measure intracellular Ca(2+) concentration ([Ca(2+)]i), we recorded [Ca(2+)]i transients and Ca(2+) sparks from isolated cardiomyocytes using confocal microscopy. The mean [Ca(2+)]i transient amplitude was significantly increased in S105N Rad TG cardiomyocytes, compared with control littermate mouse cells. The frequency of Ca(2+) sparks was also significantly higher in TG cells than in control cells, although there were no significant differences in amplitude. The sarcoplasmic reticulum Ca(2+) content was not altered in the S105N Rad TG cells, as assessed by measuring caffeine-induced [Ca(2+)]i transient. In contrast, phosphorylation of Ser(2809) on the cardiac ryanodine receptor (RyR2) was significantly enhanced in TG mouse hearts compared with controls. Additionally, the Rad-mediated RyR2 phosphorylation was regulated via a direct interaction of Rad with protein kinase A (PKA). |
