ELECTROPHYSIOLOGICAL STUDIES OF VOLTAGE GATED CHANNELS

该研究项目旨在描述和刻画 可兴奋状态下钠、钾通道的物理状态 细胞。建议用实验来研究1)电学 分子重排在经络中的表现 门控(门控电流)，2)相关的宏观电导变化 航道开闭，以及3)航道的波动 以噪声或单通道事件表示的电导。这些措施的结果 实验将在模型的帮助下分析和解释， 在这里提出的，它也将被使用(和修改)来关联 门控电流、离子电流和涨落的观测 实验。几种药物和膜改进剂将进行测试，以 完成对通道状态的描述。实验将会 使用标准的电压钳在鱿鱼巨型轴突上进行 灌流技术和新的切开轴突准备。我们建议 扩展后一种技术以允许对噪声和单次信号进行补丁记录 频道。我们的研究有望提供新的信息，说明 膜电压在物理化学水平上控制通道功能 并将有助于理解 通道在其正常运行期间。这些研究预计将包括 在神经、肌肉和其他可兴奋组织的生理学中的重要性。

The research project is aimed at the description and characterization of the physical states of the sodium and potassium channels in excitable cells. Experiments are proposed for studying 1) the electrical manifestations of the molecular rearrangements responsible for channel gating (gating currents), 2) the macroscopic conductance changes associated to channel opening and closing, and 3) the fluctuations of the channel conductance expressed as noise or single channel events. Results of these experiments will be analyzed and interpreted with the help of a model, proposed here, that will also be used (and modified) to correlate the observations on gating currents, ionic currents and fluctuation experiments. Several drugs and membrane modifiers will be tested to complete the description of the states of the channels. Experiments will be performed in squid giant axons under voltage clamp using the standard perfusion techniques and the new cut-open axon preparation. We propose to extend this latter technique to allow patch recording of noise and single channels. Our studies are expected to provide new information on how the membrane voltage controls channel function at the physico-chemical level and will help in the understanding of the structural modifications of the channel during its normal operation. These studies are expected to be of importance in the physiology of nerve, muscle and other excitable tissues.