DPCPX-resistant hypoxic synaptic depression in the CA1 region of hippocampal slices: Possible role of intracellular accumulation of monocarboxylates

Adenosine plays the principal role in synaptic depression during various energy-depleted conditions. However, additional inhibitory factors not associated with A1 adenosine receptors appear to be involved in hypoxic insults. Monocarboxylate accumulation and consequent acidic changes during hypoxia may be responsible for this remaining depression in synaptic activity. Field evoked potentials were recorded in the CA1 region of rat hippocampal slices. Preincubation with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) disclosed 43% of DPCPX-resistant synaptic depression (DRSD) during oxygen deprivation (OD). In contrast, no DRSD was detected in various conditions with limited glucose utilization, such as glucose deprivation and oxygen-glucose deprivation. Inhibition of anaerobic glycolysis (iodoacetate, sodium fluoride) abolished DRSD during OD, whereas blockade of monocarboxylate utilization with alpha-cyano-4-hydroxycinnamic acid (4-CIN) provoked DRSD in normoxic medium. These observations suggest that an intracellular accumulation of monocarboxylates is responsible for DRSD during hypoxia.