Abstract
We previously found that two types of inwardly rectifying K+ channels, homomeric Kir4.1 and heteromeric Kir4.1/5.1, differentially distributed in specific membrane domains of astrocytes, and were involved in K+ buffering. It is accompanied with Cl− flux and causes osmotic gradient, resulting in movement of water. These physiological events in astrocytes are crucial for proper regulation of neural function. AQP4 is only one water channel in astrocytes and occurs together with the Kir channels on the same membrane. Although some proteins are suggested to sort these channels to the membrane surface, the mechanism coupling the K+ and water flux remains largely unknown. Here we report that lipid raft nanodomain may scaffold K+ and water channels in astrocytes. Fractionation experiments of mouse brain revealed that the two Kir channels were expressed in lipid rafts as well as in non rafts. AQP4 distributed exclusively in lipid rafts. In kidney and transfected MDCK cells, Kir4.l and Kir5.1 were localized only in non rafts, suggesting a particular system trafficking the Kir channels to lipid rafts in the astrocytes. Moreover, whereas ClC-2 chloride channel dominates in lipid rafts with its moderate expression in non rafts, Na+,K+-ATPase and Na+,H+-exchanger were enriched in non rafts. Astrocytes' membrane may therefore possess two distinct functional platforms, i.e. lipid rafts that synchronize salt and water flux, and non rafts that transports a variety of ions. [Jpn J Physiol 55 Suppl:S128 (2005)]