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受磷蛋白调节小鼠心房收缩参数及对β-肾上腺素能激动剂的反应。

Phospholamban modulates murine atrial contractile parameters and responses to beta-adrenergic agonists.

作者信息

Kadambi V J, Koss K L, Grupp I L, Kranias E G

机构信息

Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575, USA.

出版信息

J Mol Cell Cardiol. 1998 Jul;30(7):1275-84. doi: 10.1006/jmcc.1998.0688.

Abstract

Phospholamban gene transcript levels are much lower in murine atria as compared to murine ventricles and this reduced phospholamban expression has been suggested to result in enhanced atrial contractile parameters. To delineate the functional role of phospholamban in murine atrium, the contractile parameters of isolated muscles from phospholamban knockout and cardiac-specific phospholamban overexpression mice along with their isogenic wild-type controls were evaluated. Assessment of the times (ms) to peak tension development and to half-relaxation of developed tension, as well as the rates (mg/s) of tension development and relaxation in paced atrial muscles, revealed that phospholamban ablation was associated with enhanced rates of relaxation with no significant effect on contraction rate, while phospholamban overexpression (three-fold) was associated with depressed rates of both contraction and relaxation. Isoproterenol stimulation resulted in significant increases in the rates of developed tension and relaxation in both phospholamban deficient and phospholamban overexpression atria, indicating that the beta-adrenergic pathway was functional in these muscles. These findings suggest that phospholamban is an important modulator of atrial contractility and its responses to beta-adrenergic agonists.

摘要

与小鼠心室相比,小鼠心房中的受磷蛋白基因转录水平要低得多,有人认为这种受磷蛋白表达的降低会导致心房收缩参数增强。为了阐明受磷蛋白在小鼠心房中的功能作用,我们评估了来自受磷蛋白基因敲除小鼠和心脏特异性受磷蛋白过表达小鼠的分离肌肉及其同基因野生型对照的收缩参数。对心房肌在起搏时达到张力峰值和张力减半松弛的时间(毫秒),以及张力发展和松弛的速率(毫克/秒)进行评估后发现,受磷蛋白缺失与松弛速率加快有关,对收缩速率无显著影响,而受磷蛋白过表达(三倍)与收缩和松弛速率降低有关。异丙肾上腺素刺激导致受磷蛋白缺陷型和受磷蛋白过表达型心房中张力发展和松弛的速率显著增加,表明β-肾上腺素能途径在这些肌肉中起作用。这些发现表明,受磷蛋白是心房收缩力及其对β-肾上腺素能激动剂反应的重要调节因子。

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