Na+,K+-ATPase: structure, function, and interactions with drugs.

Na+,K+-ATPase is a key element for homeostasis of sodium, potassium, and calcium ions in the nervous system and may also play a role in neurotransmitter release. Transitory changes in Na+,K+-ATPase activity occur in epileptic tissue, but this may be due to secondary compensatory processes rather than to primary events leading to epilepsy. A special role for the Na+,K+-ATPase in glial cells for controlling the concentration of extracellular potassium in normal and epileptic states remains controversial. Studies that have utilized immunocytochemical and histochemical techniques generally do not support localization of high concentrations of Na+,K+-ATPase in glial cells. A precise delineation of the structure and conformations of the Na+,K+-ATPase and sites of interaction with drugs is an important major goal of current research. Studies with fluorescent probes indicate that phenytoin exerts a major fluidizing effect on lipids of membranes, and this effect may be related in part to association of the drug with intrinsic membrane proteins.