Ion channels in regulation of excitable membranes

描述（由申请人提供）：可兴奋膜活性的改变是脊椎动物神经系统功能改变的基石。反过来，神经系统活动的改变是脊椎动物行为改变的基石。因此，了解可兴奋膜的调节有助于我们理解神经系统功能，并将这些变化与体内行为变化联系起来，为综合理解行为变化及其生物学基础提供了强有力的途径。这种研究的理想模型是弱电鱼B. pinnicaudatus，它产生电场，被称为电器官放电（EODs），用于电定位和通信。EOD波形的振幅和持续时间随环境变量的变化而变化，显然是由类固醇效应控制的。由于EOD是由电器官内所有电细胞的同步离子膜电流引起的，因此EOD波形的变化反映了单个电细胞离子电流的变化。通过确定EOD波形变化的细胞和分子机制，可以确定环境控制行为与其神经、内分泌和细胞原因之间的连续因果联系链。本项目拟采用单单元记录、双电极电压钳记录、膜片钳记录等电生理技术，探索白桦尺蠖调节这些生理变化的生理机制。该项目的具体目标是：1)将EOD的阶段与其相应的细胞外电位和细胞内动作电位联系起来；2)确定哪些离子流对细胞外电位和细胞内动作电位的两个阶段有贡献；3)确定EOD波形的快速变化在单个细胞的细胞外电位、细胞内电位和细胞内电位中表达的机制。4)确定当EOD的振幅和持续时间发生变化时，特定离子电流的变化情况。

DESCRIPTION (provided by applicant): Change in the activity of excitable membranes is a cornerstone of functional modification within the vertebrate nervous system. Modification of nervous system activity, in turn, is a cornerstone of behavioral change in vertebrates. Thus, understanding the regulation of excitable membranes contributes to our understanding of nervous system function and relating these changes to in vivo behavioral changes presents a powerful approach to an integrated understanding of behavior change and its biological bases. An ideal model for such research is the weakly electric fish, B. pinnicaudatus, which generates electric fields, known as electric organ discharges (EODs), for electrolocation and communication. The amplitude and duration of the EOD waveform varies in response to environmental variables apparently controlled by steroid effects. Because the EOD results from synchronized ionic membrane currents of all electrocytes within the electric organ, changes in EOD waveform reflect changes in ion currents of individual electrocytes. By determining the cellular and molecular mechanisms of EOD waveform change it is possible to determine a chain of continuous causal connections relating environmentally controlled behavior to its neural, endocrine, and cellular causes. The project proposed here will apply electrophysiological techniques including single unit recording, two-electrode voltage clamp, and patch-clamp recording to discover the physiological mechanisms by which B. pinnicaudatus regulate these changes inEOD. The project's specific aims are to 1) relate the phases of the EOD to its corresponding extracellular potentials and intracellular action potentials 2) determine which ion currents contribute to the two phases of the extracellular potential and to the intracellular action potential 3) determine the mechanisms by which rapid changes in EOD waveform are expressed in the extracellular potentials and intracellular potentials and intracellular potentials of individual electrocytes, and 4) determine how specific ion currents change when the EOD changes in amplitude and duration.