EFFECTS OF INCREASED EXTRACELLULAR POTASSIUM ON INFLUX OF SODIUM-IONSIN CULTURED RAT ASTROGLIA AND NEURONS

Membrane depolarization by elevated extracellular K+ concentration([K](0)) causes rapid Na+ influx through voltage-sensitive Na+ channels i nto excitable cells. The consequent increases in intracellular Na+ con centration ([Na+](i)) and/or [K+](0) stimulate Na+,K+-ATPase activity, which in turn stimulates energy metabolism and rates of glucose utili zation (CMRglc) in neurons. We previously reported that in cultured ce lls elevated [K+](0) stimulated CMRglc in neurons but not astroglia; b ut increasing [Na+](i) by opening voltage-sensitive Na+ channels with veratridine stimulated CMRglc in both. These results indicated that Na + influx plays a key role in the regulation of energy metabolism in ne urons and astroglia, but that depolarization of astroglial membranes b y elevated [K+](0) does not open voltage-sensitive Na+ channels as it does in neurons. To examine this possibility directly we have measured the effects of increased [K+](0), and of veratridine on Na+ influx in to cultured rat astroglia and neurons. Cells were incubated in bicarbo nate buffer containing ouabain (1 mM), tracer amounts of (NaCl)-Na-22, and various concentrations (5.4, 28, 56 mM) of K+ or 75 mu M veratrid ine for 0-60 min. Cells were digested and assayed for intracellular Na -22(+) content. Elevated extracellular K+ stimulated tetrodotoxin-sens itive Na-22(+) accumulation in cultured neurons but inhibited Na-22(+) influx in astroglia. Veratridine-stimulated Na+ influx in both astrog lia and neurons (144% and 133%, respectively), and these effects were completely blocked by 10 mu M tetrodotoxin. These results indicate tha t increased [K+](0) does not open voltage-sensitive Na+ channels and m ay inhibit Na+ influx in astroglia. (C) 1997 Elsevier Science B.V.