Ion Channels in Mechanosensitive Neurons

机械敏感神经元中的离子通道

• 批准号: 7150000
• 负责人: DIANA L KUNZE
• 金额: $ 28.73万
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7150000
• 关键词: Address; Afferent Pathways; Agonist; Baroreflex; Bradykinin; Calcium; Calcium Channel; Cations; Cells; Development; Family; Fiber; Gene Expression Regulation; Generations; Grant; Growth; Histamine; Imaging Techniques; Immunohistochemistry; Individual; Ion Channel; Ligands; Limb structure; Localized; Location; Membrane; Membrane Potentials; Monitor; Nervous system structure; Neurons; Neuropeptides; Nodose Ganglion; Nucleus solitarius; Pathway interactions; Pattern; Peripheral; Pressoreceptors; Presynaptic Terminals; Proteins; RNA Interference; Reflex action; Relative (related person); Research; Role playing therapy; Sensory; Sensory Receptors; Source; Substance P; Techniques; Testing; Whole-Cell Recordings; aortic arch; design; heart rhythm; member; neuronal cell body; neurophysiology; neuroregulation; pressure; receptor; response; transmission process; voltage; voltage gated channel

DESCRIPTION (provided by applicant): The long-term objective of this project is to understand the generation and transmission of mechanosensory information from the baroreceptor sensory terminal to its central termination in the nucleus of the solitary tract. This is part of a broader research effort to determine the neurophysiological and neuroanatomical substrate that underlies neural regulation of arterial pressure and cardiac rhythm. In this grant we are examining the distribution and the function of a new family of ion channels, the TRPC family of calcium permeable cation channels. These channels are important because they serve as a source of calcium influx that is expected to modulate the pattern of neuronal activity through effects on membrane potential, transmitter release at the central terminals and sensory discharge at the peripheral terminals. There are four specific aims: the first examines the distribution of the TRPC channels in the baroreceptor afferent fibers. Using immunohistochemistry, we will define the location of TRPC channels in the baroreceptor afferent pathway in three regions: the peripheral sensory receptors of myelinated and unmyelinated fibers in the arch of the aorta, in their soma in the nodose ganglion and in their synaptic terminals in the nucleus of the solitary tract. In the second aim we will ask what ligands activate these channels using an electrophysiological characterization of the channels in cell-attached patches and whole cell current in perforated patch whole cell recording. In the third aim we pursue the mechanism of activation by examining the effect of agonist on calcium influx using calcium imaging techniques to evaluate the contribution of the TRPC channels relative to the voltage-gated channels. Finally, in aim four we explore the functional consequence of activation of specific TRPC channels in whole cell voltage recording. These studies will include RNA interference to eliminate specific channels.

描述（由申请人提供）：该项目的长期目标是了解机械感觉信息从压力感受器感觉末端到孤束核中央末端的产生和传输。这是更广泛研究工作的一部分，旨在确定动脉压和心律神经调节的神经生理学和神经解剖学基础。在这笔资助中，我们正在研究一个新的离子通道家族的分布和功能，即钙渗透性阳离子通道的 TRPC 家族。这些通道很重要，因为它们是钙流入的来源，预计可以通过影响膜电位、中枢末端的递质释放和外周末端的感觉放电来调节神经元活动模式。有四个具体目标：第一个目标是检查压力感受器传入纤维中 TRPC 通道的分布。使用免疫组织化学，我们将定义 TRPC 通道在压力感受器传入通路中三个区域的位置：主动脉弓中有髓鞘和无髓鞘纤维的外周感觉受体、结状神经节的胞体以及主动脉的突触末端。孤束核。在第二个目标中，我们将使用细胞附着斑块中通道的电生理学特征和穿孔斑块全细胞记录中的全细胞电流来询问什么配体激活这些通道。在第三个目标中，我们通过使用钙成像技术检查激动剂对钙流入的影响来探索激活机制，以评估 TRPC 通道相对于电压门控通道的贡献。最后，在目标四中，我们探讨了全细胞电压记录中特定 TRPC 通道激活的功能后果。这些研究将包括 RNA 干扰以消除特定通道。