PYRUVATE and malate (P/M) increase the contribution of mitochondria to
neuronal calcium homeostasis. We have now found that cortical neurona
l cultures utilize pyruvate preferentially over glucose. The supply of
pyruvate and malate protects hippocampal and cortical neurons against
delayed cell death occurring 24 h after glutamate exposure. High [Ca2
+](i) levels attained during and after glutamate exposure were reduced
when neurons were incubated in the presence of P/M. At the single cel
l level, this was reflected in a decrease in the number of neurons tha
t respond to glutamate with high rises in [Ca2+](i) The results sugges
t that the ability to prevent large increases in [Ca2+](i) may underli
e the beneficial effects of pyruvate and malate during glutamate excit
otoxicity. (C) 1998 Rapid Science Ltd.