Potassium buffering in the central nervous system

Rapid changes in extracellular K⁺ concentration ([K ⁺]_o) in the mammalian CNS are counteracted by simple passive diffusion as well as by cellular mechanisms of K⁺ clearance. Buffering of [K⁺]_o can occur via glial or neuronal uptake of K⁺ ions through transporters or K⁺-selective channels. The best studied mechanism for [K⁺]_o buffering in the brain is called K⁺ spatial buffering, wherein the glial syncytium disperses local extracellular K⁺ increases by transferring K ⁺ ions 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 named K⁺ siphoning takes place in the vertebrate retina, where glial Müller cells express inwardly rectifying K⁺ channels (Kir channels) positioned in the 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 buffering in the CNS and recent molecular studies on the structure and functions 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.