抄録
The detergent-resistant membrane (DRM) microdomains scaffold various molecules and orchestrate signal-pathways in many cells. Although it is shown that brain astrocytes possess abundant DRM microdomains, their physiological significance is largely unknown. Here we report a novel functional role of the DRM microdomains in astroglial cells. Biochemical analysis of brain protein revealed that the K+-buffering inwardly rectifying Kir4.1 channels and the water channels AQP4, both of which are expressed specifically in astrocytes, were enriched in DRM fractions. Caveolae isolated by the caveolin-antibody did not contain either channel proteins. When coexpressed in cultured astrocytes, the immuno-staining study showed that the Kir channels and AQP4 existed in a very close vicinity and sometimes overlapped on the cell membrane. Treatment of the transfected HEK cells with methyl-β-cyclodextrin, which depletes membrane cholesterol, resulted in disappearance of Kir channels from DRM fractions and also in loss of channel-activity. In contrast, the same treatment did not affect either distribution or function of AQP4. These results may indicate that the astroglial non-caveolar DRM comprises at least two distinct components, cholesterol-dependent and -independent microdomains, each of which transports K+ or water by expressing either K+ or water channels and controlling their functionality. [J Physiol Sci. 2007;57 Suppl:S232]