Glial Maintenance of Local K+ and Neurotransmission

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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.