NITRIC OXIDE AND SARCOPLASMIC RETICULUM CA TRANSPORT

一氧化氮和肌质网 CA 运输

• 批准号: 6183487
• 负责人: MARK T ZIOLO
• 金额: $ 3.75万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6183487
• 关键词: beta adrenergic receptor; calcium channel; calcium flux; calcium transporting ATPase; cardiac myocytes; laboratory rat; neuromuscular transmission; nitric oxide; sarcoplasmic reticulum; tissue /cell culture

Nitric oxide is known to modulate cardiac contractility, however the subcellular mechanisms are unknown. There are three major regulators of cardiac contractility: L-type calcium channel (ICa), sarcoplasmic reticulum (SR), and the contractile proteins. Work has been done on the effects of NO on the ICa and the contractile proteins; however, little work has been done on the effects of NO on the SR (especially in intact myocytes). The long term objective is to understand the role of NO in cardiac excitation-contraction coupling, and thus its role in modulating cardiac contractility. The specific aims of this proposal are: 1) to determine if the anti-adrenergic effect of NO can be explained by inhibition of ICa in isolated beta-adrenergic stimulated cardiac myocytes, 2) to determine the effects of NO on specific SR calcium handling processes after beta-adrenergic stimulation (calcium handling by the ryanodine receptor (RyR), SR calcium content, and calcium uptake via the Ca-ATPase) and 3) to determine subcellular signaling mechanisms of NO mechanisms of NO regulation of SR function in isolated beta-adrenergic stimulated cardiac myocytes. The hypothesis is that NO will have an inhibitory effect on SR function (negative inotropic agent), and this effect is due to cGMP-dependent and cGMP-independent signaling pathways.

一氧化氮已知可以调节心脏收缩性，但是亚细胞机制尚不清楚。 心脏收缩性的三个主要调节剂：L型钙通道（ICA），肌质网（SR）和收缩蛋白。已经完成了NO对ICA和收缩蛋白的影响的工作。但是，对NO对SR的影响（尤其是在完整的肌细胞中）几乎没有完成的工作。 长期目的是了解NO在心脏激发控制偶联中的作用，从而在调节心脏收缩率中的作用。 The specific aims of this proposal are: 1) to determine if the anti-adrenergic effect of NO can be explained by inhibition of ICa in isolated beta-adrenergic stimulated cardiac myocytes, 2) to determine the effects of NO on specific SR calcium handling processes after beta-adrenergic stimulation (calcium handling by the ryanodine receptor (RyR), SR calcium content, and calcium uptake via the CA-ATPase）和3）确定在分离的β-肾上腺素能刺激的心肌细胞中无调节机制的亚细胞信号传导机制。 假设是，没有NO将对SR功能（负肌部剂）具有抑制作用，并且该作用是由于CGMP依赖性和与CGMP无关的信号通路所致。