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Am J Physiol. 1995 Feb;268(2 Pt 2):R506-13.

Intracellular Ca2+ transients evoked by lactic acid in cultured mammalian neurons.

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  • 1Aitken Neurosurgery Laboratory, Department of Surgery, Cornell University Medical College, New York, New York 10021.


During cerebral ischemia, accumulation of the glycolytic end product lactic acid may contribute to brain infarction. In vitro, lactic acid evokes a process of slowly evolving neuronal death characterized by a transient maintenance of cellular viability after initial injury. We examined effects of lactic acid on intracellular Ca2+ (Cai2+). Cultured neurons loaded with the fluorescent Ca2+ indicator fura 2 showed a marked increase in Cai2+ to as high as 600 nM. This increase occurred after lactic acid exposure when intracellular pH had normalized. Membrane potential was unaltered during this period, indicating that the Cai2+ increment was not a result of membrane depolarization. Increase in Ca2+ was prevented by incubating cultures in Ca(2+)-free solutions or exposing them to the L-type Ca2+ channel antagonist nimodipine. Cai2+ returned to resting levels within 20 min and remained normal during the remainder of the 4-h observation period. Neuronal Ca2+ homeostasis was disrupted after lethal exposure to lactic acid, in that subsequent exposure to 50 mM K+ failed to increase neuronal Cai2+. Cai2+ increment was integrated over a 20-min period to obtain a measure of neuronal Cai2+ load. This "calcium integral" was found to correlate directly with severity of neuronal damage observed 24 h later. Thus the Cai2+ increase integrated over time closely reflected the likelihood of lethal neuronal injury after lactic acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

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