| First Author | Glaser D | Year | 2022 |
| Journal | J Biol Chem | Volume | 298 |
| Issue | 9 | Pages | 102362 |
| PubMed ID | 35963431 | Mgi Jnum | J:333916 |
| Mgi Id | MGI:7340686 | Doi | 10.1016/j.jbc.2022.102362 |
| Citation | Glaser D, et al. (2022) Impaired myocellular Ca(2+) cycling in protein phosphatase PP2A-B56alpha knockout mice is normalized by beta-adrenergic stimulation. J Biol Chem :102362 |
| abstractText | The activity of protein phosphatase 2A (PP2A) is determined by the expression and localization of the regulatory B-subunits. PP2A-B56alpha is the dominant isoform of the B'-family in the heart. Its role in regulating the cardiac response to beta-adrenergic stimulation is not yet fully understood. We therefore generated mice deficient in B56alpha to test the functional cardiac effects in response to catecholamine administration versus corresponding wild-type (WT) mice. We found the decrease in basal PP2A activity in hearts of knockout (KO) mice was accompanied by a counterregulatory increase in the expression of B' subunits (beta and gamma) and higher phosphorylation of sarcoplasmic reticulum (SR) Ca(2+) regulatory and myofilament proteins. The higher phosphorylation levels were associated with enhanced intraventricular pressure and relaxation in catheterized KO mice. In contrast, at the cellular level, we detected depressed Ca(2+) transient and sarcomere shortening parameters in KO mice at basal conditions. Consistently, the peak amplitude of the L-type Ca(2+) current (LTCC) was reduced and the inactivation kinetics of ICaL were prolonged in KO cardiomyocytes. However, we show beta-adrenergic stimulation resulted in a comparable peak amplitude of Ca(2+) transients and myocellular contraction between KO and WT cardiomyocytes. Therefore, we propose higher isoprenaline-induced Ca(2+) spark frequencies might facilitate the normalized Ca(2+) signaling in KO cardiomyocytes. In addition, the application of isoprenaline was associated with unchanged LTCC parameters between both groups. Our data suggest an important influence of PP2A-B56alpha on the regulation of Ca(2+) signaling and contractility in response to beta-adrenergic stimulation in the myocardium. |
