Regulation of potassium by glial cells in the central nervous system

Rapid changes in extracellular K⁺ concentration ([K⁺]_o) in the mammalian central nervous system (CNS) are counteracted by simple passive diffusion as well as by cellular mechanisms of K⁺ clearance. Regulation of [K⁺]_o can occur via glial or neuronal uptake of K⁺ ions through transporters or K⁺-selective ion channels. The best studied mechanism of [K⁺]_o regulation in the brain is K⁺ spatial buffering, wherein the glial syncytium disperses local extracellular K⁺ increases by transferring K⁺ from sites of elevated [K⁺]_o to those with lower [K⁺]_o. In recent years, K⁺ spatial buffering has been implicated or directly demonstrated by a variety of experimental approaches, including electrophysiological and optical methods. A specialized form of spatial buffering termed K⁺ siphoning takes place in the vertebrate retina, where glial Müller cells express inwardly rectifying K⁺ channels (Kir channels) positioned in membrane domains near to the vitreous humor and blood vessels. This highly compartmentalized distribution of Kir channels in retinal glia directs K⁺ ions from the synaptic layers to the vitreous humor and blood vessels. Here, we review the principal mechanisms of [K⁺]_o regulation in the CNS and recent molecular studies on the structure and function of glial Kir channels. We also discuss intriguing new data that suggest a close physical and functional relationship between Kir and water channels in glial cells.