G PROTEIN MODULATION OF N-TYPE CALCIUM CHANNELS

N 型钙通道的 G 蛋白调节

• 批准号: 6391686
• 负责人: Victor Ruiz-Velasco
• 金额: $ 4.56万
• 依托单位: GUTHRIE FOUNDATION FOR EDUCATION AND RES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-22 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6391686
• 关键词: G protein; calcium channel; inhibitor /antagonist; laboratory rat; neural transmission; protein protein interaction; protein structure function; sympathetic nervous system; voltage gated channel; western blottings

DESCRIPTION: (Applicant's Description) The long-term goal of this research proposal is to gain an understanding of the molecular events associated with the modulation of N-type Ca2+ channels by Gbetagamma subunits. The main hypothesis to be tested is that the subunit composition of the Gbetagamma dimer, i.e., specific combinations of Gbeta and Ggamma confer specificity in regard to voltage-dependent N-type Ca2+ channel modulation. Accordingly, the specific aims are 1) to identify which G protein beta subunit produces voltage-dependent N-type Ca2+ channel inhibition in rat sympathetic neurons; 2) to determined which G protein betagamma combinations confer specificity for voltage-dependent N-type Ca2+ channel modulation; and 3) to identify the G protein beta and gamma subunits that are natively expressed in rat sympathetic neurons by employing the Western blotting method. By employing electrophysiological, molecular, and biochemical methods, the role of the Gbetagamma composition in modulation of Ca2+ channels will be delineated and better understood. Voltage-dependent modulation of N-type Ca2+ channels has been demonstrated in a wide variety of neurons from both the central and peripheral nervous system. Although most studies are performed on the neuron soma, there is evidence from direct studies of nerve terminals to support the idea that this form of modulation plays an important role in presynaptic mechanisms of synatic transmission. Thus there is substantial interest in furthering our understanding of the molecular events which contribute to N-type Ca2+ channel modulation.

描述：（申请人的描述） 这项研究建议的长期目标是了解 与N型Ca2+通道调节有关的分子事件 Gbetagamma亚基。要测试的主要假设是亚基 Gbetagamma二聚体的组成，即Gbeta和Gbeta的特定组合 Ggamma会议授予依赖电压的N型Ca2+通道的特异性 调制。因此，具体目的是1）确定哪种G蛋白 β亚基在大鼠中产生依赖电压的N型Ca2+通道抑制 同情神经元； 2）确定哪种G蛋白betagamma组合 依赖电压依赖性n型Ca2+通道调制的特异性； 3） 识别G蛋白β和伽马亚基的本质表达 在大鼠交感神经元中采用蛋白质印迹法。经过 采用电生理，分子和生化方法， CA2+通道调制中的Gbetagamma组成将被描述 并更好地理解。 N型Ca2+通道的电压依赖性调制已在A中证明 来自中央和周围神经系统的各种神经元。 尽管大多数研究都是对神经元躯体进行的，但仍有证据 直接研究神经终端，以支持这种形式 调制在突触前机理中起重要作用 传播。因此，人们对进一步发展我们的兴趣很大 了解有助于N型Ca2+通道的分子事件 调制。