ION CHANNELS

感觉加工与简单和复杂的表达 行为依赖于不同部分之间的快速通信 神经系统。这是通过电可兴奋细胞来实现的。 通过电信号对信息进行编码和传输。电气 兴奋性反映了电压门控离子通道的活性 响应电压变化而打开，允许离子流过 细胞膜。兴奋性的性质取决于门控 这些渠道的行为、数量、类型和空间分布 薄膜。这些属性的更改已牵涉到 在发育过程中观察到的兴奋性的改变，如下 神经损伤神经的疾病或损伤详细了解该功能和 在分子水平上调节离子通道是前提条件 对显影过程中控制电刺激性的认识 病态系统。这将需要应用 电生理、遗传和分子生物学技术 电压门控离子通道的研究。一个强大的系统，在这个系统中 这些方法中可以使用的是果蝇。在本计划书中，重点是 关于钠和钙通道，果蝇神经元和肌管和 通过以下途径鉴定在其表达中重要的基因 突变体的生理分析。我已经确定了三个基因，Para， Sei和TIP-E，它们改变了胚胎的宏观钠电流 神经元。我的生理实验表明，Para编码是一种 功能性钠通道蛋白，与ITS序列一致 与脊椎动物的钠通道基因相似。虽然SEI和TIP-E 也可能编码钠通道，它们可能是 调节兴奋性的其他方面，如数量或分布 频道。进一步分析这些和其他基因座的突变 发现在全细胞和单个细胞上都影响钠通道 通道水平对于理解这些基因的作用非常重要 在钠离子通道中表达。除了钠，钙离子还有 可兴奋电池中重要的电荷载体。因此，我建议 检查野生型神经元和肌管中的钙通道。基因 参与钙通道表达的基因将使用 我们开发的用于检测染色体缺失的缺乏症筛查 改变了全细胞钙电流的表达。结果是 这些研究将定义和表征重要的分子 离子通道在电活动中的作用和调节 兴奋性。

Sensory processing and the expression of both simple and complex behaviors depend on rapid communication between disparate parts of the nervous system. This is accomplished by electrically excitable cells that encode and transmit information via electrical signals. Electrical excitability reflects the activity of voltage-gated ion channels that open in response to changes in voltage, allowing the flow of ions across the cell membrane. The properties of excitability depend on the gating behavior, number, type and spatial distribution of these channels in the membrane. changes in these properties have been implicated in modifications of excitability observed during development, following disease or injury to a nerve. A detailed knowledge of the function and regulation of ion channels at the molecular level is prerequisite to understanding the control electrical excitability in developing or pathological systems. This will require the application of electrophysiological, genetic, and molecular biological techniques to the study of voltage-gated ion channels. A powerful system in which all of these approaches can be used is Drosophila. In this proposal focus on sodium and calcium channels Drosophila neurons and myotubes and characterization of genes important in their expression through physiological analysis of mutants. I have identified three genes, para, sei, and tip-E, which alter the macroscopic sodium currents in embryonic neurons. My physiological experiments suggest that para codes for a functional sodium channel protein, consistent with its sequence similarity to a vertebrate sodium channel gene. Although sei and tip-E may also code for sodium channels, they may instead be genes which regulate other aspects of excitability such as number or distribution of channels. Further analysis of mutations at these and additional loci found to affect sodium channels, both at the whole-cell and single channel level will be important in understanding the role of these genes in sodium channel expression. In addition to sodium, calcium ions are important charge carrier in excitable cells. I therefore propose to examine calcium channels in wildtype neurons and myotubes. Genes involved in expression of calcium channels will be identified using a deficiency screen that we have developed to detect chromosomal deletions that alter the expression of whole-cell calcium currents. The results of these studies will define and characterize the molecules important in the function and regulation of ion channels involved in electrical excitability.