グリア細胞のK⁺・水輸送を担うチャネルの局在制御とその分子基盤

抄録

The brain astrocytes transport excess extracelluar K⁺ yielded by synaptic activation to regions of low K⁺ uni-directionally. This called "K⁺ buffering" is accompanied with water flux. Physiological coupling of these fluxes is essential for proper brain function. Inwardly rectifying K⁺ (Kir) channels are assumed to be crucial for K⁺ buffering. We found two types of Kir channels, homomeric Kir4.1 and heteromeric Kir4.1/5.1, distributed on astrocytic membranes and were involved in K⁺ buffering. Perivascular processes harbor the heteromer, which would secrete K⁺, and perisynaptic processes differentially express either channel in a region specific manner, which may play a distinct role in K⁺ uptake. Because activity of Kir4.1/5.1 is dynamically regulated by intracellular pH (pH_i) change in a physiological range, K⁺ outflow and part of K⁺ influx may be finely controlled by pH_i. We further found that the two Kir channels occurred together with AQP4, only one water channel in astrocytes, at the same membrane surface of the processes. Dystrophin associated protein complex could specifically target the Kir and water channels to the perivascular processes. Moreover, we have identified that "lipid raft" microdomain selectively gathers not only apparatuses responsible for water and K⁺ transport such as Kir4.1, Kir5.1 and AQP4 but also other molecules including astroglical Cl⁻ channel ClC-2 and glutamate transporter GLT-1. Accordingly, lipid rafts may serve as a functional microplatform synchronizing salt, water, and glutamate transports in astrocytes. [J Physiol Sci. 2006;56 Suppl:S10]