Voltage-dependent ion channels in glial cells.

Glial cells, although non-excitable, express a wealth of voltage-activated ion channels that are typically characteristic of excitable cells. Since these channels are also observed in acutely isolated cells and in brain slices, they have to be considered functional in the intact brain. Numerous studies over the past 10 years have yielded detailed characterizations of glial channels permitting comparison of their properties to those of their neuronal counterparts. While for the most part such comparisons have demonstrated a high degree of similarity, they also provide evidence for the expression of some uniquely glial ion channels. An increasing number of studies indicate that the expression of "glial" channels is influenced by the cells' microenvironment. For example, the presence of neurons can induce or inhibit (depending on the preparation and type of channel studied) the expression of glial ion channels. Like ion channels in excitable cells, glial channels can be functionally regulated by activation of second-messenger pathways, allowing for short-term modulation of their membrane properties. Although the extent to which most of the characterized ion channels are involved in glial function is presently unclear, a growing body of data suggests that certain channels play an active role in glial function. Thus inwardly rectifying K+ channels in concert with delayed rectifying K+ channels are thought to be involved in the removal and redistribution of excess K+ in the brain, a process referred to as "spatial buffering". Glial K+ channels may also be crucial in modulating glial proliferation. Cl- channels and stretch-activated cation channels are believed to be involved in volume regulation. Na+ channels appear to be important in fueling the glial Na+/K(+)-pump, and Ca2+ channels are likely involved in numerous cellular events in which intracellular Ca2+ is a critical second messenger.