Regulation of Neuronal Calcium Channels

神经元钙通道的调节

• 批准号: 8682329
• 负责人: AMY LEE
• 金额: $ 41.18万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 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/8682329
• 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

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Cav通道介导基因转录和神经传递所需的活性依赖性Ca 2+信号。Ca 2+依赖性失活和易化（分别为CDI和CDF）允许Cav通道根据神经元活性调节Ca 2+内流，从而微调控制神经元兴奋性和突触可塑性的Ca 2+信号。这项研究的基本原理是，定义Cav通道如何产生和维持Ca 2+信号将回答长期存在的关于Cav通道在神经元中的异质性的问题，并使新的机制探究特定Cav通道在协调神经系统的正常发育和功能中的作用。拟议研究的预期成果是：建立钙视黄蛋白作为效应物（包括Cav2.1）的动态调节剂的新作用（Aim 1）;阐明负责神经元Cav 1 L型电流的“持久”特性和功能影响的机制（Aim 2）。我们相信，拟议的研究将产生持久和积极的影响：它将定义的Cav通道调节机制可能会促进神经元Ca 2+信号失调引起的神经和神经精神疾病的新疗法的开发。