Molecular substrates of potassium spatial buffering in glial cells.

Abstract

It is generally accepted that the foremost mechanism for the buffering of K+ from the extracellular space ([K+]o) in the brain is "K+ spatial buffering." This is the process by which glial cells dissipate local K+ gradients by transferring K+ ions from areas of high to low [K+]o. These glial K+ fluxes are mediated mainly by inwardly rectifying K+ (Kir) channels. The K+ spatial buffering hypothesis has been tested and confirmed in the retina, in which is has been termed as "K+ siphoning". In Müller cells, the primary glial cells of the retina, Kir channels are distributed in a highly non-uniform manner, exhibiting high concentrations in membrane domains facing the vitreous humor (endfeet) and in proximity to the blood vessels (perivascular processes). Such nonuniform distribution of Kir channels facilitates directed K+ fluxes in the retina from the synaptic plexiform layers to the vitreous humor and blood vessels. Recent molecular and electrophysiological studies in Müller cells have revealed a high degree of complexity in terms of Kir channel subunit composition, mechanisms of subcellular localization, and regulation. How such complexity fits into their proposed role in buffering [K+]o in retina is the main topic of this article.