Phorbol ester alters rat hippocampal neuronal response to hypoxia

The effect of the protein kinase C (PKC) activator, 4β-phorbol-12,13-dibutyrate (β-PDBu) on electrophysiological properties of rat hippocampal CA1 neurons exposed to moderate hypoxia was examined. Hypoxic β-PDBu-pretreated neurons differed from untreated neurons by exhibiting an adenosine-independent loss of synaptic transmission, an apparent large increase in injected threshold current necessary to elicit an action potential, an increase rather than a decrease in membrane resistance, and an increase rather than a decrease in hyperpolarizing holding current. Additional experiments with an adenosine A1 antagonist suggest that β-PDBu alters neuronal responses to hypoxia through some mechanism other than the documented ability of β-PDBu to uncouple the A1 receptor.