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INVESTIGATOR PROFILES |
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SENIOR SCIENTIST CONTACT |
Min Zhou, M.D., Ph.D.Research FocusAstrocytes are one of the major glial cell types in the mammalian central nervous system (CNS) that provide critical structural, metabolic and homeostatic support to the principle brain cell, neurons. Initial proposal for the homeostatic function of astrocytes has been based on the observations that astrocytes do not generate electrical impulses, a means that is employed by their neuronal counterpart in CNS for information processing, but express a unique type of membrane potassium (K+) conductance activating independent of membrane potential. This potassium conductance not only enables astrocytes to tightly regulate extracellular potassium concentration within a low physiological level (K+-buffering), but also establishes a rather negative astrocyte membrane potential that optimizes the function of transporters/exchangers expressed abundantly in astrocytes so that neuron activation induced fluctuation neurotransmitter concentrations in extracellular space can be maintained at a nontoxic level. Dr. Zhou is interested in the molecular identification of potassium channels that give rise to voltage-independent astrocyte potassium conductance. Involvement of a family of potassium channels, namely, the two-pore domain K+ channels (K2Ps), has been a current focus of research. The study is attempting to identify specific K2P species that are expressed by astrocytes, to determine how change in these K2Ps could possibly affect astrocyte homeostatic function, and whether and how neurotransmitters, such as glutamate and GABA, interact with K2Ps of various kinds of mechanisms that integrate neuronal information processing with astrocyte homeostatic function. Dr. Zhou is also interested in the pathological involvement of astrocyte potassium channels in cerebral ischemia. The research has been currently focused on the acute responses of astrocyte K2Ps to ischemic insults. Future research has been conceived to understand how ischemic insults induce altered expression of astrocyte K2P as mechanisms regulating astrocyte homeostatic support to the survival neurons outside of the server ischemic infarct area, with a hope that the resulted knowledge will inspire novel thinking for clinical intervention on the stroke outcome. Astrocytes are extensively coupled through intercellular gap junction channels as syncytium. Study aiming at physiological understanding of electrical coupling among astrocytes and changes under ischemia conditions has been another focus of current research. Early glial electrophysiology study conducted by Dr. Zhou in rat hippocampus demonstrated the existence of heterogeneous glial populations that share more or less the same star-like morphology, but differ in a variety of functional protein expressions, namely, ion channels, glutamate receptors and transporters. The observation together with studies by others has led to the conclusion that traditionally defined astrocytes can be further divided into functionally diverse subpopulations. It becomes increasingly clear that a subpopulation of glial cells that can be recognized by membrane marker NG expression should be considered as a new member in the glial family. Dr. Zhou’s research has continued in this direction to understand the lineage relationship of NG2 glia with other CNS constituents and the function of NG2 glia. To achieve these research goals, Dr. Zhou and his coworkers at the Ordway Research Institute have applied in situ electrophysiology to examine the functional ion channels, receptors and transporters; have employed immunocytochemical confocal microscopy techniques to identify critical protein expression; and have used molecular biology, e.g., RT-PCR, to identify the genes encoding these functional proteins. Selected Publications (View)
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