Glial ion transport and volume control.

K(+)-induced glial swelling results from an intricate interaction of transport and diffusion processes and metabolic stimulation, with many open questions remaining. Our concept of the major mechanisms involved can be summarized as follows: high extracellular K+ causes a burst-like stimulation of Na+/K+ ATPase and, hence, increases the metabolic demands. Lactate is produced; the cell is slightly acidified. To maintain a normal intracellular pH, the Na+/K+ antiporter extrudes protons and supplies Na+ for further Na+/K+ exchange. In addition, K+ ions enter the cell via membrane channels or furosemide-inhibitable transport. K+, Cl-, and lactate- ions accumulate as the osmotic basis for cell swelling. Later, cell volume normalizes slowly, a process involving lactate export and other, so far unidentified mechanisms. Taken together, the temporary swelling of glia at high K+ concentrations is the result of a homeostatic function, for the maintenance of a constant extracellular potassium concentration. Ion control ranges over volume control. In pathophysiologic states the loss of cell volume regulation may become a clinical problem, if cerebral swelling leads to an increase in intracranial pressure. It should be kept in mind, however, that elevation of the extracellular K+ concentration is not the only cause of glial swelling. Tissue acidosis, the release of neurotransmitters, especially glutamate, or free fatty acids are other mediator mechanisms initiating the swelling of glial elements. Only under controlled in vitro conditions can the individual significance of these factors be evaluated on a quantitative basis. Therapeutic approaches should be selected very carefully in order to maintain homeostatic mechanisms that are of utmost importance, especially after an insult to the brain.