RESTING POTENTIAL IN NERVE MEMBRANE

我们建议将联合收割机电生理测量和 放射性同位素通量测量，以研究控制机制 神经膜的静息电位。 目前， 对静息态的转运机制知之甚少， 电流（决定静息电位）。 我们的初步 研究表明，静息电位是由一个 一种新型的电压门控静息通道， 延迟整流器K通道的特性。 具体 本研究的目的是：（1）识别和 表征控制细胞膜的膜途径， 静息状态下的膜电流;（2）为了彻底测试 现有的电扩散理论（即Goldman-Hodgkin-Katz (GHK)方程），同时测量膜 电位、膜电导和膜渗透性 作为离子浓度的函数。 这些实验将 在可激发离子通道和 离子泵被堵塞;（3）开发改进的理论 模型的静息电位，将观察到的 静息通路进入电- 扩散理论 我们希望这项研究能够提供一个 更好的模型，这将解释实验结果更多 比GHK方程更令人满意 鱿鱼巨大的轴突将被用作主要的生物模型。 该制备具有若干技术优点。 例如，在一个示例中， 使用内部灌注技术，内部和 轴突的外部离子环境可以随意控制。 单向同位素标记的离子通量也可以是 直接测量，几乎没有歧义。 此外，这种 测量可以在恒定的膜电位下进行， 使用电压和空间钳位。 药物干预是 可用于阻断可激发离子通道和离子泵。 与我们 专门设计的仪器，一些实验 可以同时测量参数（例如， 电导和在给定膜电位下的42 K流出）。 等 同步测量将使我们能够彻底测试 理论模型，通过比较从不同的 方法.

We propose to combine electrophysiological measurements and radioisotope flux measurements to study the control mechanisms of the resting potential of the nerve membrane. At present, very little is known about the transport mechanisms of the resting current (which determines the resting potential). Our preliminary studies have indicated that the resting potential is controlled by a new type of voltage-gated resting channel which differs in properties from the delayed rectifier K channel. The specific aims of this proposed research are: (1) To identify and to characterize the membrane pathways which control the membrane current at the resting state; (2) To thoroughly test the existing electro-diffusion theory (i.e. the Goldman-Hodgkin-Katz (GHK) equation) by simultaneously measuring membrane potential, membrane conductance and membrane permeabilities as a function of ionic concentrations. These experiments will be done under the condition that the excitable ionic channels and the ion pumps are blocked; (3) To develop an improved theoretical model of the resting potential by incorporating the observed transport properties of the resting pathways into the electro- diffusion theory. We hope this research will be able to provide a better model which will explain the experimental findings more satisfactorily than the GHK equation. The squid giant axon will be used as the primary biological model. This preparation has several technical advantages. For example, using an internal perfusion technique, both the internal and external ionic environment of the axon can be controlled at will. The unidirectional isotope-labelled ion fluxes can also be measured directly with little ambiguity. Furthermore, such measurements can be done at a constant membrane potential by using voltage-and space-clamp. Pharmacologic interventions are available to block excitable ion channels and ion pumps. With our specially designed apparatus, a number of experimental parameters can be measured simultaneously (e.g. membrane conductance and 42K efflux at a given membrane potential). Such simultaneous measurements will allow us to thoroughly test the theoretical model by comparing data obtained from different methods.