Glutamine currents in hippocampal neurons are attributable to contaminating glutamate

Physiological responses of cultured rat hippocampal neurons to exogenously applied glutamine were studied using tight-seal, whole-cell voltage clamp techniques in nominal extracellular magnesium. Four mM glutamine induced peak inward currents which were 4.6 +/- 1.7% (+/- 1 S.D.) of current responses to 100 microM glutamate. Ten microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 1 mM magnesium, 20 microM MK-801, and 200 microM D-aminophosphonovalerate (APV) blocked these responses in a pattern similar to N-methyl-D-aspartate antagonism. Current-voltage plots produced by 4 mM glutamine and 10 microM glutamate were identical. Even in the absence of extracellular magnesium, 4 mM glutamine was not toxic to our cultured neurons. The data suggest that physiological responses to glutamine are attributable to low concentrations of glutamate in commercial preparations and that glutamine alone has insignificant physiological and toxic effects.