The Role of Phospholipase C in Hair Cell Inhibition

磷脂酶 C 在毛细胞抑制中的作用

• 批准号: 6551766
• 负责人: SUCHITRA IYER
• 金额: $ 3.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6551766
• 关键词: acetylcholine; biological signal transduction; calcium channel; calcium flux; cochlea; ear hair cell; immunocytochemistry; intracellular transport; laboratory rat; neural inhibition; neurophysiology; neuroregulation; nicotinic receptors; phospholipase C; polymerase chain reaction; postdoctoral investigator; potassium channel; receptor coupling; second messengers; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): In vertebrate outer hair cells, synaptic inhibition is achieved by the activation of nicotinic (ionotropic) acetylcholine (ACh) receptors that usually mediate excitatory postsynaptic responses else where in the nervous system. Calcium (Ca++) influx through these ACh receptors leads to activation of calcium dependent potassium channels. This proposal aims to explore the intracellular pathways that couple the ionotropic hair cell ACh receptors to inhibition. A combination of electrophysiology and molecular biology techniques will be used to test whether an IP3-sensitive calcium store may be involved in such a process. Since phospholipase C (PLC) catalyses the synthesis of IP3, the role of PLC in cholinergic inhibition will be examined next by employing pharmacological agents. RT-PCR and immunohistochemistry will used to determine the pattern of expression of the different PLC sub-types in the cochlea. Data from this research will help elucidate the molecular mechanisms by which ACh released from the olivo-cochlear bundle mediates hair cell inhibition.

描述（由申请人提供）：在脊椎动物的外毛细胞中，突触抑制是通过激活烟碱（离子型）乙酰胆碱（ACh）受体来实现的，该受体通常介导神经系统其他部位的兴奋性突触后反应。钙 (Ca++) 通过这些 ACh 受体流入，导致钙依赖性钾通道激活。该提案旨在探索将离子型毛细胞乙酰胆碱受体耦合到抑制作用的细胞内途径。电生理学和分子生物学技术的结合将被用来测试 IP3 敏感的钙储存是否可能参与这一过程。由于磷脂酶 C (PLC) 催化 IP3 的合成，因此接下来将通过使用药物来检查 PLC 在胆碱能抑制中的作用。 RT-PCR 和免疫组织化学将用于确定耳蜗中不同 PLC 亚型的表达模式。这项研究的数据将有助于阐明从橄榄耳蜗束释放的乙酰胆碱介导毛细胞抑制的分子机制。