SUBUNIT INTERACTIONS IN L-TYPE CALCIUM CHANNELS

L型电压激活钙通道是一种异源多聚体 由成孔α 1亚基和辅助亚基组成的蛋白质 分别是贝塔阿尔法2德尔塔和伽马虽然电生理 研究表明，这些辅助亚基是至关重要的， 通道特性的决定因素，生物化学和分子事件 这些亚基之间相互作用的基础在很大程度上是未知的。的 拟议的研究将解决这一假设， 参与附件对通道特性的调节 亚单位。双杂交系统将用于确定涉及的领域 在蛋白质相互作用中。随后，功能 将在哺乳动物细胞中评估这些相互作用的意义 表达系统，其中多种免疫学、药理学和生物学的方法可以在表达系统中表达。 电生理学方法可用于评估通道 性能和通道功能。这一多学科方法将 进一步了解钙通道的机制 亚基关联，以及随后的通道功能。临床上 相互作用域阐明将有助于检索以鉴定新的 药理学靶点，由此Ca通道可以在治疗上 操纵，这将是非常有益的，因为广泛的频谱 疾病，特别是中枢神经系统疾病， 钙稳态。

L-type voltage activated calcium (Ca) channels are heteromultimeric proteins composed of a pore-forming alpha1 subunit and accessory subunits known as Beta, alpha2, delta, and gamma. Though electrophysiological studies have demonstrated that these accessory subunits are critical determinants of channel properties, the biochemical and molecular events underlying the interaction of these subunits is largely unknown. The proposed studies will address the hypothesis that multiple interactions are involved in the modulation of channel properties by accessory subunits. The two-hybrid system will be used to identify domains involved in protein-protein interactions. Subsequently, the functional significance of these interactions will be assessed in a mammalian cell expression system where a variety of immunological, pharmacological, and electrophysiological approaches can be used to evaluate channel properties and channel function. This multidisciplinary approach will lend further understanding into the mechanisms underlying Ca channel subunit associations, and consequently, channel function. Clinically, the elucidation of interacting domain will aid searches to identify novel pharmacological targets whereby Ca channels may be therapeutically manipulated, which would be extremely beneficial given the wide spectrum of disorders, particularly in the CNS, which are associated with changes in Ca homeostasis.