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Keywords:

  • astrocytes;
  • K+ channels;
  • methyl-β-cyclodextrin;
  • water channels

Abstract

The detergent-resistant microdomains (DRM) of cell membranes scaffold different molecules and regulate cell functions by orchestrating various signaling pathways including G-proteins and tyrosine kinase. Here we report a novel role for DRM in astroglial cells. K+-buffering inwardly rectifying Kir4.1 channels and the water channel AQP4 are expressed in astrocytes and they may be functionally coupled to maintain ionic and osmotic homeostasis in the brain. Kir4.1 and AQP4 channel proteins were abundant in noncaveloar DRM in the brain and also in HEK293T cells when exogenously expressed. In HEK293T cells, depletion of membrane cholesterol by methyl-β-cyclodextrin (MβCD) resulted in loss of Kir4.1 association with DRM and its channel activity but did not affect either the distribution or the function of AQP4. Immunolabeling showed that Kir4.1 and AQP4 were occasionally distributed in close proximity but in distinct compartments of the astroglial cell membrane. Astroglial noncaveolar DRM may therefore be made up of at least two distinct compartments, MβCD-sensitive and MβCD-resistant microdomains, which control localization and function of, respectively, Kir and AQP4 channels on the cell membrane.