Regulation of extracellular K+ and pH by polarized ion fluxes in glial cells: The retinal Muller cell

Muller cells, the principal glial cells of the retina, exhibit a high degree of functional and morphological polarization. An inward rectifying K+ channel, the dominant ion channel in Muller cells, is localized preferentially to cell endfeet, which terminate on the vitreal surface of the retina and on blood vessels. Two acid/ base transport systems, an Na+/HCO3- cotransporter and a Cl-/HCO3- anion exchanger, also are localized preferentially to the endfeet. These functional specializations facilitate the ability of Muller cells to regulate extracellular ion levels in the retina. Muller cells regulate extracellular K+ levels by transporting K+ away from the neural retina to the vitreous humor and the subretinal space, Muller cells may also regulate retinal CO2 and pH by the combined action of cell carbonic anhydrase and acid/base transporters localized to the endfeet, and they may control blood flow by the depolarization-induced release of potassium and protons from cell endfeet onto blood vessels. The physiology of ion transport in CNS astrocytes is not understood as well as it is in Muller cells. The presence of inward rectifying K+ channels and acid/base transporters in astrocytes, however, suggests that these cells may utilize mechanisms similar to those of Muller cells in regulating the extracellular microenvironment and in controlling blood flow.