Mechanisms of K+ Channel Modulation in Plasticity

K 通道可塑性调制机制

• 批准号: 6687714
• 负责人: Laura Schrader
• 金额: $ 13.91万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-17 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6687714
• 关键词: Xenopus oocyte; biological signal transduction; calcium binding protein; electrophysiology; enzyme activity; gene expression; hippocampus; immunocytochemistry; laboratory rabbit; laboratory rat; mutant; neural information processing; neural plasticity; neuroregulation; neurotransmitter receptor; phosphorylation; potassium channel; protein kinase; protein protein interaction; protein structure function; pyramidal cells; site directed mutagenesis; synapses; voltage /patch clamp; western blottings

DESCRIPTION (provided by applicant): K+ channels play a critical role in basic neuronal function, and represent a substrate through which neuronal activity can dynamically regulate the excitability and firing properties of neurons. This proposal is designed to determine the role of phosphorylation in functional modulation of the protein subunits that constitute K+ channels. Activation of various kinases, specifically PKA, CaMKII, PKC and ERK/MAPK can initiate phosphorylation of K+ channels, and these kinases are activated by various second messenger systems that are coupled to neurotransmitter receptors. Thus, the regulation of K+ channels by kinase activation may not only play a role in information processing and storage that occurs during learning and memory, but also during the normal signal integration of synaptic transmission. This project builds on the recent discovery that voltage gated transient K+ currents in particular strongly modulate hippocampal neuron excitability and information processing. Kv4.2 is a Shal-type K+ channel subunit protein that is localized to pyramidal neuron dendrites and physiological and pharmacological evidence suggests that Kv4.2 is the pore-forming subunit of the Shal-type channels. The Kv4.2 subunits associate with a family of interacting proteins, the K+ Channel Interacting Proteins (KChIPs) in the hippocampus. The KChIPs are a family of Ca2+ binding proteins that are 99 percent homologous to a characterized transcription repressor. The interaction of the Kv4.2 and KChIP subunits provides multiple substrates for kinase phosphorylation to functionally regulate the channels. In addition, the Ca2+-binding properties of KChIP convey a possible role for Kv4.2 and KChiPs in Ca2+ mediated plasticity. This proposal will determine the role of phosphorylation of IC channel subunits in the dynamic regulation of K+ currents. Specifically, we will study the biophysical properties of wild-type and phosphorylation-site mutant channels through electrophysiological recordings in oocytes. In addition, we will study their modulation in hippocampal neurons, assayed by biochemical and immunohistochemical techniques.

描述（申请人提供）：K+通道在基础中起着至关重要的作用