Glial Maintenance of Local K+ and Neurotransmission

描述（由申请人提供）：细胞外K+ ([K+]o)的轻度增加抑制了神经元的兴奋性和突触通讯。在中风、脑外伤和癫痫发作时，会出现较大的[K+]o升高，导致神经元缺陷。在正常和病理生理条件下，中枢神经系统中的星形胶质细胞通过一种尚不清楚的被动机制协助缓冲[K+]o。内校正K+通道（KIRs）被认为负责被动K+稳态，并由海马星形胶质细胞表达。这一建议将回答有关星形胶质细胞kir在海马中的内源性功能的基本问题。星形胶质细胞膜片钳记录将确定钡敏感刺激引起的K+电流的生理特性。共聚焦显微镜和免疫细胞化学将用于确定kir在海马星形胶质细胞膜上的定位。星形胶质细胞体细胞和过程的膜片钳记录，以及K+成像技术，将确定kir在响应神经元刺激时携带局部内向K+电流的能力。这些研究将确定KIRs在海马星形胶质细胞中的功能相关性，并为KIRs在被动[K+]o缓冲中的作用提供新的见解。

DESCRIPTION (provided by applicant): Neuronal excitability and synaptic communication are depressed by mild increases in extracellular K+ ([K+]o). During stroke, brain trauma, and seizures, large [K+]o rises occur, causing neuronal deficits. Under normal and pathophysiological conditions, astrocytes in the CNS assist in buffering [K+]o by passive mechanisms that are not well understood. Inwardly-rectifying K+ channels (KIRs) are thought to be responsible for passive K+ homeostasis, and are expressed by hippocampal astrocytes. This proposal will answer fundamental questions concerning the endogenous function of astrocyte KIRs in the hippocampus. Astrocyte patch-clamp recordings will determine the physiological properties of barium-sensitive stimulus evoked K+ currents. Confocal microscopy and immunocytochemistry will be used to determine the localization of KIRs on hippocampal astrocyte membranes. Patch-clamp recordings from astrocyte somas and processes, along with K+ imaging techniques, will determine the capacity for KIRs to carry localized inward K+ currents in response to neuronal stimulation. These studies will determine the functional relevance of KIRs in hippocampal astrocytes and provide new insight into the role of KIRs in passive [K+]o buffering.