CALCIUM CHANNELS IN SYMPATHETIC NEURONS

交感神经元中的钙通道

• 批准号: 2431260
• 负责人: KEITH S ELMSLIE
• 金额: $ 9.46万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2431260
• 关键词: Rana; adenosine triphosphate; animal extract; antineoplastics; calcium channel; calcium channel blockers; creatine phosphate; guanosine triphosphate; hormone regulation /control mechanism; neural inhibition; neurons; neuropharmacology; norepinephrine; okadaic acid; sympathetic nervous system; voltage /patch clamp; voltage gated channel

Voltage-gated calcium channels are important for neuronal functions such as neurotransmitter release and electrical excitability. Neurotransmitters can regulate these functions by effecting calcium channel gating. The long term goal of the proposed research is to understand the gating of neuronal calcium channels and how this gating is modulated by neurotransmitters to effect changes in neuronal activity. This proposal is focused on the N-type calcium channel in frog sympathetic neurons. N-channels are involved in neurotransmitter release and neurotransmitter inhibition of synaptic release has been correlated with the inhibition of N-type calcium current. The N-channel is the dominate calcium channel in sympathetic neurons and N-current has been well described at the macroscopic level. However, little is known about single N-channel gating. In addition, our evidence suggests that the N- channel was misidentified in previous studies from frog sympathetic neurons. The goals of the project are to examine the gating properties of the N-type calcium channel and determine the effect of neurotransmitters on N-channel gating. Toward these goals, we have identified a calcium channel which has the characteristics expected for the N-channel and differs from previously recorded 'N'-channels. Some of the questions which will be addressed are: (1) What are the criteria for the identification of single N-channels? (2) Do N-channels show modal gating like some other calcium channels? (3) What gating processes underlie N-channel inactivation? (4) How is N-channel gating altered by neurotransmitters to produce voltage-dependent inhibition? In addition, other calcium channels present in sympathetic neurons will be identified and characterized as they are encountered. This will allow us to better understand their role in the physiology of sympathetic neurons. This study is focused on the N-channel, but the process used in calcium channel identification will facilitate future work on neurons with a more complex mix of calcium channels. In addition, the knowledge gained about single N-channel gating will be important for the development of comprehensive models on calcium-dependent synaptic release and how that release can be inhibited by neurotransmitters.

电压门控钙通道对于神经元功能很重要 作为神经递质释放和电兴奋性。 神经递质可以通过钙来调节这些功能 通道门控。 拟议研究的长期目标是 了解神经元钙通道的门控以及该门控 由神经递质调节以实现神经元活性的变化。 该提案的重点是青蛙中的N型钙通道 交感神经元。 N通道参与神经递质释放 神经递质抑制突触释放已相关 随着N型钙电流的抑制。 N通道是 交感神经元中的钙通道和n-电流中的占主导地位一直是 在宏观水平上进行了很好的描述。 但是，对 单个N通道彩控。 此外，我们的证据表明n- 在青蛙同情的先前研究中，渠道被误认为 神经元。 该项目的目标是检查门控属性 N型钙通道的 N通道门控的神经递质。 朝向这些目标，我们有 确定了一个具有预期的特征的钙通道 N通道和与先前记录的“ N'-通道”有所不同。 一些 将要解决的问题是：（1）标准是什么 用于识别单个N通道？ （2）做N通道显示 像其他一些钙通道一样，模态门控？ （3）什么门控过程 基础n通道失活？ （4）如何改变N通道门控 神经递质产生电压依赖性抑制作用？ 此外， 还将确定同情神经元中存在的其他钙通道 并在遇到时被描述。 这将使我们变得更好 了解它们在交感神经元生理中的作用。 这项研究的重点是N通道，但是钙用于钙的过程 渠道识别将促进更多的神经元的工作 钙通道的复杂混合物。 此外，知识获得了 单n通道门控对发展至关重要 有关钙依赖性突触释放的综合模型以及如何 神经递质可以抑制释放。