MODULATION OF POTASSIUM CHANNELS IN DROSOPHILA

描述：本提案将检查信令模块是否用于 细胞内信使与细胞内钾通道的共定位 乙醚-A-GO-GO(EAG)家族通过测定生理重要性 果蝇生理和行为中与EAG相关的信号模块。 信号模块在EAG电流调节中的作用将是 通过在异源表达中共表达单个成分来检查(A) 系统，并使用电压钳位和贴片检查产生的电流 钳夹技术，以及(B)通过电生理记录神经和 幼虫神经肌肉连接处的肌肉活动。来自正常的录音 苍蝇将被与从突变体中获得的苍蝇进行比较，在突变体中， 信令模块已被删除或正常关联被中断。 观察到的电生理缺陷对过度兴奋性的影响 和其他行为，特别是通过求爱测试的学习 条件性试验，也将进行检查。除了连接机构之外， 渠道调制对行为的改变，这些研究将提供证据 对于一种可能的机制，通过这种机制，细胞内动作的特异性 酶是可以实现的。一旦理解，这一机制就可以用作 治疗药物的目标将比目前的药物更具体 受雇于治疗一些心理和神经肌肉疾病 精神错乱。

DESCRIPTION: This proposal will examine whether signaling modules serve to co-localize intracellular messengers with potassium channels of the ether-a-go-go (EAG) family by determining the physiological importance of EAG-associated signaling modules in the physiology and behavior of Drosophila. The role of signaling modules in the regulation of EAG currents will be examined (a) by co-expressing individual components in heterologous expression systems and examining the resulting currents using voltage clamp and patch clamp techniques, and (b) by electrophysiological recordings of nerve and muscle activity at the larval neuromuscular junction. Recordings from normal flies will be compared to those obtained from mutants in which components of the signaling modules have been deleted or the normal associations disrupted. The consequences of observed electrophysiological defects for hyperexcitability and other behaviors, specifically learning as assayed using a courtship conditioning assay, will also be examined. In addition to linking mechanisms of channel modulation to changes in behavior, these studies will provide evidence for one possible mechanism by which the specificity of action of intracellular enzymes can be achieved. Once understood, this mechanism can be used as a target for therapeutic agents that will be more specific than those currently employed in the treatment of a number of psychological and neuromuscular disorders.