G PROTEIN MODULATION OF N-TYPE CALCIUM CHANNELS

描述：（申请人的描述） 本研究提案的长期目标是了解 与N型Ca 2+通道调节相关的分子事件 γ亚单位。要检验的主要假设是， γ-二聚体的组成，即，Gbeta和 G γ对电压依赖性N型钙通道具有特异性 调变因此，具体的目标是：1）鉴定哪种G蛋白 β亚单位对大鼠N型钙通道的电压依赖性抑制作用 交感神经元; 2）确定哪些G蛋白β-γ组合 赋予电压依赖性N型Ca 2+通道调节的特异性;和3） 鉴定天然表达的G蛋白β和γ亚基， 用Western blotting方法检测大鼠交感神经元的神经元凋亡。通过 采用电生理学、分子和生物化学方法， 将描绘在调节Ca 2+通道中的γ-射线组成 更好地理解。 N型Ca 2+通道的电压依赖性调节已经在一项研究中得到证实。 来自中枢和外周神经系统的各种神经元。 虽然大多数研究都是在神经元索马上进行的，但有证据表明， 直接研究神经末梢，以支持这种形式的想法， 调制在突触前机制中起着重要的作用 传输因此，有很大的兴趣，进一步我们的 对N型钙通道分子事件的理解 调变

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.