THE MOLECULAR BASIS OF MEMBRANE EXCITABILITY

这项拟议的研究的目标是了解电学 神经和心脏信号的功能和调节 离子通道。电压钳位技术用于测量 流经这些通道的电流响应于电和 化学刺激。钠离子和钙离子的调节作用 神经递质和激素所产生的钙通道 分离的神经细胞原代培养的研究 心肌细胞。 在这个实验室中，已经发现β-肾上腺素能刺激可以 实质上增加了至少一种类型的 脊椎动物感觉神经元中发现的钠通道。这一发现 尤其重要，因为电压门控钠通道 在病毒的启动和传播中起着至关重要的作用 神经、肌肉和心肌细胞的细胞电信号。 因此，因为钠通道是导致 动作电位、激素或神经递质的时相 钠通道功能的调节可能起到基础性作用 在调节细胞电活动中的作用。全细胞 电压钳技术将被用来研究离子 钠电流增加背后的通道机制。在……里面 此外，电压钳位测量结合 将使用药物学和生化技术来探测 调节反应的细胞机制。实验 来确定这一幽默的共性 钠通道的调制，通过确定：1)程度到 该调制发生在相同的其他小区类型中 以及2)这种调节在多大程度上发生在其他 动物的种类。钙离子通道的调节 腺苷将在培养的神经元和心脏细胞中进行研究。 将应用电气和生化技术来探测 调节这种调节反应的细胞机制。 对钠、钙动态调节的认识 通道功能对于理解复合体是必不可少的 健康神经元和心脏细胞的电活动。它还将 对了解神经或神经功能改变有重要意义 心脏疾病，并应帮助发展 疾病治疗干预的药理学策略 可兴奋的组织。

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.