논문 초록

The Molecular Mechanism of Neuronal Activity-dependent Volume Regulation by Astrocytes
It has been hypothesized that astrocytes take up extracellular K+, then swell, and restore to normal volume with extrusion of Cl- and osmolytes such as glutamate and taurine during neuronal activity. Despite numerous studies, the exact molecular mechanism of volume regulation has not been established yet. To investigate this hypothesis, we recorded the optical intrinsic signal (OIS) evoked by repetitive electrical stimulation, cell volume and fEPSP in mouse hippocampal slice. We found that OIS is dependent on neuronal activity, and that the time course of OIS correlated well with the volume in astrocyte. However, there was no change of volume in neuron. Many studies suggested that NKCC1 might play a role in K+ uptake and astrocyte swelling. However, we found that deletion of NKCC1 gene does not affect increase in volume. To measure K+ movement during volume increase, we performed the K+ imaging and found the K+ influx in astrocyte and efflux in neuron. These are abolished by the blocking of AMPAR and NMDAR mediated K+ efflux using CNQX and APV. It has been suggested that extrusion of Cl- and osmolytes via VRAC is important for decrease in volume. However, we found that Best1 known as Ca2+-activated anion channel in astrocytes is critically involved in activity-dependent volume decrease using conditional gene knock-down system via lentiviral Best1 shRNA. We found an impairment of volume decrease by general silencing of Best1 and recovery by astrocyte-specific gene rescue of Best1.
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