Effects of increased extracellular potassium on influx of sodium ions in cultured rat astroglia and neurons

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.