@entity4854 reduces functional expression of astrocytic @entity24248 channels and glial XXXX uptake.

@entity3529 @entity3264 @entity64 @entity6 @entity413 @entity302 @entity972 @entity35 @entity4854 @entity24248 @entity2359 @entity385
UNASSIGNED: @entity6 are at risk for a number of serious health complications including an increased incidence of @entity302 and poorer recovery after @entity385 . Astrocytes play a critical role in protecting neurons by maintaining extracellular homeostasis and preventing @entity2359 through @entity3264 uptake and @entity972 buffering. These functions are aided by the presence of @entity972 channels, such as @entity24248 inwardly rectifying @entity972 channels, in the membranes of astrocytic glial cells. The purpose of the present study was to determine if @entity4854 alters @entity24248 @entity972 channel expression and homeostatic functions of astrocytes. We used q-PCR, Western blot, patch-clamp electrophysiology studying voltage and @entity972 step responses and a colorimetric @entity3264 clearance assay to assess @entity24248 channel levels and homeostatic functions of @entity35 astrocytes grown in normal and high @entity413 conditions. We found that astrocytes grown in high @entity413 (25mM) had an approximately 50% reduction in @entity24248 mRNA and protein expression as compared with those grown in normal @entity413 (5mM). These reductions occurred within 4-7days of exposure to @entity4854 , whereas reversal occurred between 7 and 14days after return to normal @entity413 . The decrease in functional Kir channels in the astrocytic membrane was confirmed using barium to block Kir channels. In the presence of 100- M barium, the currents recorded from astrocytes in response to voltage steps were reduced by 45%. Furthermore, inward currents induced by stepping extracellular [ @entity3529 ]o from 3 to 10mM (reflecting @entity972 uptake) were 50% reduced in astrocytes grown in high @entity413 . In addition, @entity3264 clearance by astrocytes grown in high @entity413 was significantly impaired. Taken together, our results suggest that down-regulation of astrocytic @entity24248 channels by elevated @entity413 may contribute to the underlying pathophysiology of @entity6 and contribute to the poor prognosis after @entity64 .
