ERK Regulation of Hippocampal Potassium Channels

海马钾通道的 ERK 调节

• 批准号: 6936799
• 负责人: SHARI G BIRNBAUM
• 金额: $ 3.97万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-18 至 2006-02-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936799
• 关键词: action potentials; antibody; biological signal transduction; dendrites; enzyme activity; genetically modified animals; hippocampus; immunologic substance development /preparation; laboratory mouse; laboratory rat; learning; long term memory; long term potentiation; membrane activity; mitogen activated protein kinase; neural plasticity; phosphorylation; postdoctoral investigator; potassium channel; protein protein interaction; synapses

DESCRIPTION (provided by applicant): ERK/MAPK activation is a critical component of the signaling mechanisms that regulate synaptic plasticity and the formation of long-term memories in a large variety of species. The substrates for ERK phosphorylation that contribute to the induction of LTP and long-term memory formation are largely unknown. One intriguing possibility is the potassium channel, Kv4.2, which forms a transient A-type potassium current (IA) in pyramidal neurons of the hippocampus and regulates membrane excitability. ERK activation decreases IA and enhances the amplitude of back-propagating action potentials in pyramidal cell dendrites. These changes may play an important role in mediating learning-related neuronal plasticity in the brain. This proposal will investigate the role of ERK phosphorylation of Kv4.2 in the hippocampus in the formation of memories and modulation of synaptic plasticity. Antibodies to phosphorylated Kv4.2 will be developed and used to assess any changes in ERK-mediated Kv4.2 phosphorylation following induction of LTP as well as a hippocampus-dependent learning task, contextual fear-conditioning. The role of Kv4.2 in synaptic plasticity and learning and memory will be further evaluated using Kv4.2 knockout mice. This research will enhance our understanding of the molecular changes that support learning and synaptic plasticity, as well as provide insights into disease states such as mental retardation.

描述（由申请人提供）：ERK/MAPK激活是调节突触可塑性的信号传导机制的关键组成部分，并在各种物种中形成了长期记忆。有助于LTP诱导和长期记忆形成的ERK磷酸化的底物在很大程度上未知。一种有趣的可能性是钾通道KV4.2，它在海马的金字塔神经元中形成了瞬态A型钾电流（IA），并调节膜兴奋性。 ERK激活减少了IA并增强了锥体细胞树突中后传播作用电位的幅度。这些变化可能在介导大脑中与学习相关的神经元可塑性中起重要作用。该建议将研究KV4.2在海马形成中的ERK磷酸化和突触可塑性调节中的作用。将开发和用于评估ERK介导的KV4.2磷酸化LTP以及海马依赖性学习任务后的ERK介导的KV4.2磷酸化的任何变化的抗体，以评估ERK介导的KV4.2磷酸化。 KV4.2在突触可塑性，学习和记忆中的作用将使用KV4.2基因敲除小鼠进一步评估。这项研究将增强我们对支持学习和突触可塑性的分子变化的理解，并提供对诸如智力低下的疾病状态的见解。