Regulation of Neuronal Calcium Channels

神经元钙通道的调节

基本信息

批准号：
8807195
负责人：
AMY LEE
金额：
$ 3.65万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-15 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8807195
关键词：
Animal Model Anxiety Ataxia Attention deficit hyperactivity disorder Autistic Disorder Basic Science Behavior Behavioral Binding Binding Proteins Biochemical Bipolar Disorder Brain Brain Diseases Buffers Calcium Channel Calmodulin Cardiac Cardiovascular Diseases Cells Cytoplasmic Granules Development Disease Drosophila genus Epilepsy Exhibits Feedback Fright Genes Genetic Genetic Polymorphism Genetic Transcription Ions Knowledge Learning Macromolecular Complexes Major Depressive Disorder Mediating Migraine Molecular Mus Mutation Nervous System Physiology Neurologic Neuromuscular Junction Neurons Outcome P-Q type voltage-dependent calcium channel Pathogenesis Pharmacologic Substance Physiological Process Property Recruitment Activity Regulation Research Risk Factors Role Schizophrenia Signal Transduction Synaptic Transmission Synaptic plasticity System Testing Therapeutic United States National Institutes of Health Work base behavioral impairment caldendrin calretinin cell type computer studies effective therapy genetic manipulation in vivo information processing insight loss of function motor control nervous system disorder neuronal excitability neurophysiology neuropsychiatry neurotransmission novel novel therapeutics programs public health relevance research study sensor voltage

项目摘要

DESCRIPTION (provided by applicant): Voltage-gated Cav channels mediate activity-dependent Ca2+ signals required for gene transcription and neurotransmission. Ca2+-dependent inactivation and facilitation (CDI and CDF, respectively) allow Cav channels to adjust Ca2+ influx according to neuronal activity, thereby fine-tuning Ca2+ signals that control neuronal excitability and synaptic plasticity. The rationale for the proposed research is that defining how Cav channels generate and maintain Ca2+ signals will answer longstanding questions regarding the heterogeneous properties of Cav channels in neurons and enable new mechanistic inquiries into the roles of specific Cav channels in orchestrating the normal development and function of the nervous system. The expected outcomes of the proposed research are: establishment of a new role for calretinin as a dynamic regulator of effectors including Cav2.1 (Aim 1); and elucidation of a mechanism responsible for the "long-lasting" properties and functional impact of neuronal Cav1 L-type currents (Aim 2). We believe that the proposed research will make a lasting and positive impact: the Cav channel regulatory mechanisms it will define will likely facilitate the development of novel therapeutics for neurological and neuropsychiatric disorders resulting from dysregulation of neuronal Ca2+ signals.

描述（由申请人提供）：电压门控的CAV通道介导了基因转录和神经传递所需的活动依赖性CA2+信号。 Ca2+依赖性失活和促进（分别为CDI和CDF）允许CAV通道根据神经元活性来调整Ca2+流入，从而微调控制神经元兴奋性和突触可塑性的CA2+信号。拟议的研究的理由是，定义CAV通道如何生成和维护CA2+信号将回答有关神经元中CAV通道异质性质的长期问题，并启用对特定CAV通道在策划正常发育和神经系统功能的作用的新机械询问。拟议的研究的预期结果是：为钙蛋白素建立新作用，成为cav2.1在内的效应子的动态调节剂（AIM 1）；并阐明了负责神经元CAV1 L型电流的“持久”特性和功能影响的机制（AIM 2）。我们认为，拟议的研究将产生持久的积极影响：它将定义的CAV通道调节机制可能会促进神经元CA2+信号失调引起的神经和神经精神疾病的新型治疗剂的开发。