THE MOLECULAR BASIS OF MEMBRANE EXCITABILITY

这项研究的目的是为了了解电 神经和心脏信号的功能和调节 离子通道。 电压钳技术用于测量 通过这些通道的电流响应于电和 化学刺激 钠离子功能的调节， 钙通道的神经递质和激素将 在分离的神经元的原代培养物中研究， 心肌细胞 在这个实验室中，已经发现β-肾上腺素能刺激 基本上增加至少一种类型的导电性， 在脊椎动物感觉神经元中发现钠通道。 这一发现 因为电压门控钠通道 在启动和传播中起着至关重要的作用， 神经、肌肉和心脏细胞的细胞电信号。 因此，由于钠通道负责升高 动作电位、激素或神经递质的相位 钠离子通道功能的调节可能在 调节细胞电活动的作用。 全细胞 电压钳技术将用于研究离子 通道机制的基础上增加钠电流。 在 此外，电压钳测量结合 药理学和生物化学技术将用于探测 调节反应的细胞机制。 实验 将进行，以确定这种体液的一般性， 钠通道的调节，通过确定：1） 这种调节发生在相同的其他细胞类型中， （2）这种调节在其他物种中发生的程度 动物的种类。 钙离子通道的调节 将在培养的神经元和心脏细胞中研究腺苷。 电和生物化学技术将被应用于探测 调节这种调节反应的细胞机制。 了解钠和钙的动态调节 通道功能对于理解复杂的 健康神经元和心脏细胞的电活动。 它还将 对于理解神经或神经系统的功能改变是很重要的， 心脏病，并应有助于发展 用于疾病治疗干预的药理学策略 兴奋性组织。

The goal of the proposed research is to understand the electrical signals of nerve and heart in terms of the function and regulation of ionic channels. Voltage clamp techniques are used to measure the current through these channels in response to electrical and chemical stimuli. The modulation of the function of sodium and calcium channels by neurotransmitters and hormones will be investigated in primary cultures of dissociated neuronal and cardiac cells. In this laboratory, beta-adrenergic stimulation has been found to substantially increase the conductance of at least one type of sodium channel found in a vertebrate sensory neuron. This finding is especially significant since the voltage-gated sodium channel plays an essential role in the initiation and propagation of the cellular electrical signals of nerve, muscle and cardiac cells. Thus, because the sodium channel is responsible for the rising phase of the action potential, hormonal or neurotransmitter modulation of sodium channel function may play a fundamental role in modulating cellular electrical activity. The whole-cell voltage clamp technique will be used to investigate the ionic channel mechanisms underlying the increase in sodium current. In addition, voltage clamp measurements combined with pharmocological and biochemical techniques will be used to probe the cellular mechanisms mediating the response. Experiments will be carried out to determine the generality of this humoral modulation of sodium channels, by determining: 1) the extent to which this modulation occurs in other cell types of the same species; and 2) the extent to which this modulation occurs in other species of animals. The modulation of calcium channels by adenosine will be studied in cultured neurons and heart cells. Electrical and biochemical techniques will be applied to probe the cellular mechanisms mediating this regulatory response. Understanding the dynamic regulation of sodium and calcium channel function is essential to an understanding of the complex electrical activity of healthy neurons and heart cells. It will also be important to the understanding of altered function in neural or cardiac disease, and should aid in the development of pharmacological strategies for therapeutic intervention in disease of excitable tissues.