Ion channels in regulation of excitable membranes

描述（由申请人提供）：可兴奋膜活性的变化是脊椎动物神经系统功能改变的基础。反过来，神经系统活动的改变是脊椎动物行为变化的基石。因此，了解可兴奋膜的调节有助于我们了解神经系统功能，并将这些变化与体内行为变化联系起来，为综合了解行为变化及其生物学基础提供了一种强有力的方法。这种研究的理想模型是弱电流鱼B。pinnicaudatus，其产生电场，称为电器官放电（EOD），用于电定位和通信。EOD波形的幅度和持续时间随环境变量的变化而变化，显然受类固醇效应的控制。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，EOD波形的变化反映了单个电细胞离子电流的变化。通过确定爆炸物处理波形变化的细胞和分子机制，有可能确定一系列连续的因果关系，将环境控制行为与其神经、内分泌和细胞原因联系起来。本研究拟应用单细胞记录、双电极电压钳、膜片钳等电生理技术，探讨B. pinnicaudatus调节这些变化在EOD。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）确定哪些离子电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波形的快速变化在细胞外电位和细胞内电位中表达的机制，单个电细胞，以及4）确定当EOD在幅度和持续时间上改变时特定离子电流如何改变。

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.