MODULATION AND REGULATION OF NEURONAL CALCIUM CHANNELS

电压门控性钙通道在细胞凋亡中起关键作用。 调节所有可兴奋细胞的细胞功能。 第一，CA 2 + 通过通道的进入对于 电信号转化为特定的细胞反应， 神经递质释放和激素分泌，调节 通过钙激活离子通道的兴奋性，收缩， 基因转录的调控，等等。第二，由于它们的 电压依赖性，通道是重要的元素 有助于细胞的兴奋特性。 最近的电生理学和药理学实验 证明电压门控钙通道构成了一个 不同但相关的蛋白质家族。 钙的三种类型 在背根神经节（DRG）中已经表征了通道 细胞，并已被称为L-，N-和T-型。 信道类型 它们的时间和电压依赖性不同， 药理学特性 他们也可能负责 不同的功能反应。 神经科学中的一个基本问题是， 调节递质和神经调质的释放。 的作用 分泌过程中不同类型的钙通道将 在本提案中，通过以下方式进行评估： l）利用膜片钳记录技术来表征 存在于神经制备物中的钙通道类型 终末和内分泌细胞系中; 2)研究钙通道活性的调节， 递质/神经调质及其相关的第二信使 这些准备工作中的系统; 3)用放射免疫分析技术监测激素释放 同时控制钙通道的活动 神经系统中的所有信号都是由电 在神经元中转化为化学信息的脉冲 突触 由于通道是这种电传导的基础， 对于化学信号来说，关于它们属性的信息是至关重要的， 了解正常和异常神经系统的各个方面 功能

Voltage-gated calcium channels play a critical role in the regulation of cellular function in all excitable cell. First, CA2+ entry through the channel is crucial to the tranduction of electrical signals into specific cellular responses including neurotransmitter release and hormone secretion, regulation of excitability via Ca-activated ionic channels, contraction, regulation of gene transcription, etc. Second, because of their voltage-dependent properties, the channels are important elements contributing to the excitable properties of cells. Recent electrophysiological and pharmacological experiments have demonstrated that voltage-gated calcium channels constitute a family of diverse, but related, proteins. Three types of calcium channels have been characterized in dorsal root ganglion (DRG) cells and have been termed L-, N-, and T-types. The channel types vary in their time-and voltage-dependent properties, and pharmacological properties. They may also be responsible for different functional responses. One of the fundamental questions in neuroscience concerns the regulation of transmitter and neuromodulator release. The role of the different types of calcium channels in secretory processes will be assessed in this proposal by: l) utilizing patch clamp recording techniques to characterize the types of calcium channels present in a preparation of nerve terminals and in an endocrine cell line; 2) studying the modulation of calcium channel activity by transmitters/neuromodulators and their associated second messenger systems in these preparations; 3) monitoring hormone release with radioimmunoassay techniques while manipulating calcium channel activity. All signalling in the nervous system consists of electrical impulses which are translated into chemical messages at neuronal synapses. Since channels underlie this transduction of electrical to chemical signals, information about their properties is critical to understanding all aspects of normal and abnormal nervous system function.