Since capillaries appear not to contribute significantly to rapid removal of K ϩ from brain tissue, the K ϩ released into extracellular clefts by neurons at the onset of electrical activity is presumably removed either by redistribution in the clefts or by uptake into cells. What appear to be the three major processes require no energy from the glial cells. These are diffusion through the extracellular clefts, spatial buffering by glial cells, and net uptake of K ϩ into glial cells through glial K ϩ channels associated with uptake of Cl Ϫ through an independent Cl -conductance. There is a relatively slow uptake by the Na ϩ /K ϩ -ATPase, which directly consumes ATP. In addition, some glial cells take up K ϩ on the Na ϩ /K ϩ /2Cl -cotransporter, which leads indirectly to energy consumption when the Na ϩ is subsequently pumped out.
Currently available data suggest that the glial energy metabolism devoted to K ϩ homeostasis is less than a tenth of the total tissue energy metabolism, even under conditions of pathologically high extracellular [K ϩ ]. Hence, in situ, it is possible that glial cells could function with much less ATP than neurons do.
All the various routes of muffling of changes in extracellular [K ϩ ] can be modulated, directly or indirectly, by transmitters liberated by neurons. A consequence of this could be regulation of the entry of Na ϩ into glial cells such that the Na ϩ /K ϩ -ATPase is activated. The degree of activation might be adjusted so that the resulting activation of the glial glycolytic pathway is appropriate to the provision of the quantity of metabolic substrates required by the neurons.