Saxitoxin Tetrodotoxin and the Metabolism and Cation Fluxes in Isolated Cerebral Tissues

Saxitoxin and tetrodotoxin at low concentrations (10 −7 ‐10 −8 M) exerted similar inhibitory effects on the increase in lactate production and the redistrjbution of Na + and K + that normally accompany electrical stimulation of rat cerebral cortical slices. In contrast, the toxins exerted dissimilar effects on the production of lactate in response to low concentrations of Ca 2+ in the medium. Inhibition by tetrodotoxin occurred at a higher concentration of Ca 2+ and was significantly greater than that produced by saxitoxin at concentrations of Ca 2+ below 0.75 mM. These differences were not related to differential effects on the redistribution of Na + and K + under such conditions. The toxins had different effects on Ca 2+ influx. Tetrodotoxin, but not saxitoxin, inhibited the influx of Ca 2+ in the absence of electrical stimulation. The influx of Ca 2+ increased when electrical pulses were applied and tetrodotoxin inhibited this increase, whereas saxitoxin potentiated influx of Ca 2+ during stimulation. Our results suggest that metabolic responses to conditions that increase excitability are not governed solely by changes in the distribution of Na + and K + . The differential effects of the toxins on Ca 2+ fluxes suggest that one site of Ca 2+ entry during electrical stimulation may be functionally independent of Na + entry.