ION CHANNELS IN MECHANOSENSITIVE NEURONS

机械敏感神经元中的离子通道

• 批准号: 6125977
• 负责人: DIANA L KUNZE
• 金额: $ 21.5万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6125977
• 关键词: action potentials; antisense nucleic acid; baroreceptors; baroreflex; confocal scanning microscopy; electrophysiology; immunocytochemistry; in situ hybridization; mathematical model; membrane potentials; membrane structure; neuroregulation; polymerase chain reaction; potassium channel; vascular smooth muscle nervous control; voltage gated channel

We are studying the expression of voltage-gated ion channels in the soma and terminals of baroreceptor neurons whose mechanosensitive terminals lie in the adventitia of walls of major arteries. We have proposed that these channels underlie the markedly different firing patterns of the receptors connected to unmyelinated versus myelinated fibers as they respond to changes in arterial pressure. In particular, this proposal focuses on the identification, followed by functional assessment, of the specific voltage-gated potassium channels. These channels shape the action potential and discharge patterns and they are frequent targets of neuromodulators. In the first aim we will determine which of the members of the potassium channel families, Kvl, Kv2, Kv3 and Kv4, are present in the soma of baroreceptor neurons through the use of RT-PCR, in situ hybridization and channel specific antibodies. In aim two we will move to the peripheral terminal, the actual baroreceptor, to ask whether the channels that are present in the soma are also present on the peripheral terminals. We will use immunocytochemical techniques to explore the distribution of the ion channels within the terminals of both myelinated and unmyelinated fibers using confocal microscopy. In Aim 3 we will examine the functional role of the specific potassium channels. To do this we are using anti-sense strategy in identified baroreceptor neurons. The contributions of a distinct channel to resting membrane potential, action potential and to the discharge produced by depolarization will be examined. Finally, in Aim 4 we will tie together the electrophysiological characterization with anatomical localization of the channels identified in AIMS 1-3 in mathematical models that allow us to make testable predictions for the role of each of these channels A and C baroreceptor neurons.

我们正在研究压力感受器神经元的躯体和末端的电压门控离子通道的表达，其机械敏感末端位于主要动脉壁的外来。 我们已经提出，这些通道是与无髓纤维相关的髓鞘纤维相关的受体的显着发射模式的基础，它们在响应动脉压的变化时。 特别是，该提案着重于对特定电压门控钾通道的识别，然后进行功能评估。 这些通道塑造了动作电位和放电模式，它们是神经调节剂的频繁目标。 在第一个目的中，我们将通过使用RT-PCR，原位杂交和通道特定的抗体来确定钾通道家族的哪些成员KVL，KV2，KV3和KV4存在于Baroroceptor神经元的soma中。 在目标二中，我们将移至外围终端，即实际的压力感受器，询问SOMA中存在的通道是否也存在于外围端子上。 我们将使用免疫细胞化学技术探索使用共聚焦显微镜在髓鞘和不髓鞘纤维末端内的离子通道的分布。 在AIM 3中，我们将检查特定钾通道的功能作用。 为此，我们在确定的压力感受器神经元中使用了反敏感策略。 将研究一个独特的通道对静息膜电位，动作电位和去极化产生的排放的贡献。 最后，在AIM 4中，我们将将电生理表征与数学模型中AIMS 1-3中鉴定的通道的解剖学定位联系在一起，这使我们能够对这些通道A和C Barorecector神经元的每个通道的作用做出可测试的预测。