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，这些受体通常介导神经系统中的其他兴奋性突触后反应。通过这些ACH受体的钙（Ca ++）涌入会导致钙依赖性钾通道的激活。该提案旨在探索将离子毛细胞ACH受体融入抑制的细胞内途径。电生理学和分子生物学技术的结合将用于测试IP3敏感钙储存是否可能参与此过程。由于磷脂酶C（PLC）催化了IP3的合成，因此接下来将通过使用药理剂来检查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子类型的表达模式。这项研究的数据将有助于阐明ACH从Olivo-Cochlear束释放的分子机制介导了毛细胞的抑制作用。