GI PROTEIN MEDIATED LOCALIZATION OF B2-AR SIGNALING IN RAT CARDIOMYOCYTES

GI 蛋白介导的大鼠心肌细胞中 B2-AR 信号传导的定位

• 批准号: 6097806
• 负责人: M KUSCHEL
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6097806
• 关键词: G protein; beta adrenergic receptor; biological signal transduction; heart cell; heart contraction; laboratory rat; muscle cells; pertussis toxin; phospholamban; phosphorylation; protein localization; receptor expression; sarcolemma; tissue /cell culture

Recent studies have shown that the cardiac b2-adrenoceptor (b2-AR) contractile response is mediated by a localized cAMP/protein kinase (PKA)-dependent augmentation of L-type Ca2+ current (ICa) and occurs in the absence of PKA-mediated phosphorylation of more remote proteins, e.g. phospholamban (PLB), an important modulator of cardiac relaxation. Since b2-AR is also coupled to Gi proteins, and pertussis toxin (PTX) augments the contractile response following b2-AR stimulation, we hypothesized that Gi might be involved in the localization of b2-AR signaling. Thus, we examined the effect of PTX on the kinetics of b2-AR mediated site-specific PLB phosphorylation and relaxation in rat cardiomyocytes. PTX enhanced the effect of the b2-AR agonist zinterol (Zin, 10-5 M) on contraction amplitude and rescued its relaxation effect, whereas the b1-AR mediated response remained unchanged. Zin induced a cAMP-dependent PLB phosphorylation in a time and dose-dependent manner (EC50=48.6+/-1.8 nM) only in PTX-treated cardiomyocytes, with a maximal increase in phosphorylation by 6.5-fold, similar to that induced by the b1-AR agonist norepinephrine (37.9+/-4.7 and 36.7+/-7.7, respectively). Therefore, the coupling of b2-AR to Gi proteins is a key factor for the localization of b2-AR signaling to a subsarcolemmal domain and this constraint can be removed by PTX.

最近的研究表明，心脏

项目成果

Involvement of NMDA receptors containing the GluN2C subunit in the psychotomimetic and antidepressant-like effects of ketamine.

• DOI: 10.1038/s41398-020-01110-y
• 发表时间: 2020-12-10
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Tarrés-Gatius M;Miquel-Rio L;Campa L;Artigas F;Castañé A
• 通讯作者: Castañé A