Membrane depolarization by elevated extracellular K+ concentration ([K+](o)) causes rapid Na+ influx through voltage-sensitive Na+ channels into excitable cells. The consequent increases in intracellular Na+ concentration ([Na+](i)) and/or [K+](o) stimulate Na+,K+-ATPase activity, which in turn stimulates energy metabolism and rates of glucose utilization (CMR(glc)) in neurons. We previously reported that in cultured cells elevated [K+](o) stimulated CMR(glc) in neurons but not astroglia; but increasing [Na+](i) by opening voltage-sensitive Na+ channels with veratridine stimulated CMR(glc) in both. These results indicated that Na+ influx plays a key role in the regulation of energy metabolism in neurons and astroglia, but that depolarization of astroglial membranes by elevated [K+](o) 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+](o) and of veratridine on Na+ influx into cultured rat astroglia and neurons. Cells were incubated in bicarbonate buffer containing ouabain (1 mM), tracer amounts of 22NaCl, and various concentrations (5.4, 28, 56 mM) of K+ or 75 μM veratridine for 0-60 min. Cells were digested and assayed for intracellular 22Na+ content. Elevated extracellular K+ stimulated tetrodotoxin-sensitive 22Ns+ accumulation in cultured neurons but inhibited 22Ns+ influx in astroglia. Veratridine-stimulated Na+ influx in both astroglia and neurons (144% and 133%, respectively), and these effects were completely blocked by 10 μM tetrodotoxin. These results indicate that increased [K+](o) does not open voltage-sensitive Na+ channels and may inhibit Na+ influx in astroglia.
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