| First Author | Saadeh K | Year | 2020 |
| Journal | Ann N Y Acad Sci | Volume | 1478 |
| Issue | 1 | Pages | 63-74 |
| PubMed ID | 32713021 | Mgi Jnum | J:299886 |
| Mgi Id | MGI:6490780 | Doi | 10.1111/nyas.14426 |
| Citation | Saadeh K, et al. (2020) Protein expression profiles in murine ventricles modeling catecholaminergic polymorphic ventricular tachycardia: effects of genotype and sex. Ann N Y Acad Sci 1478(1):63-74 |
| abstractText | Catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with mutations in the cardiac ryanodine receptor (RyR2). These result in stress-induced ventricular arrhythmic episodes, with clinical symptoms and prognosis reported more severe in male than female patients. Murine homozygotic RyR2-P2328S (RyR2(S/S) ) hearts replicate the proarrhythmic CPVT phenotype of abnormal sarcoplasmic reticular Ca(2+) leak and disrupted Ca(2+) homeostasis. In addition, RyR2(S/S) hearts show decreased myocardial action potential conduction velocities (CV), all features implicated in arrhythmic trigger and substrate. The present studies explored for independent and interacting effects of RyR2(S/S) genotype and sex on expression levels of molecular determinants of Ca(2+) homeostasis (CASQ2, FKBP12, SERCA2a, NCX1, and CaV 1.2) and CV (NaV 1.5, Connexin (Cx)-43, phosphorylated-Cx43, and TGF-beta1) in mice. Expression levels of Ca(2+) homeostasis proteins were not altered, hence implicating abnormal RyR2 function alone in disrupted cytosolic Ca(2+) homeostasis. Furthermore, altered NaV 1.5, phosphorylated Cx43, and TGF-beta1 expression were not implicated in the development of slowed CV. By contrast, decreased Cx43 expression correlated with slowed CV, in female, but not male, RyR2(S/S) mice. The CV changes may reflect acute actions of the increased cytosolic Ca(2+) on NaV 1.5 and Cx43 function. |
