Decreased large conductance Ca2+-activated K+ channel activity in dissociated CA1 hippocampal neurons in rats exposed to perinatal and postnatal hypoxia

Abstract

Hypoxia is a major cause of neonatal encephalopathy and seizures, and an increased neuronal excitability may be an underlying mechanism. To determine the role of Ca2+-activated K+ channels in hyperexcitability, we measured large unitary conductance (>200 pS, BKCa) currents in symmetrical 140/140 mM K+ using inside-out configuration in CA1 pyramidal cells acutely dissociated from the hippocampus of rats exposed to normoxia or hypoxia (at 10% inspired O2) for 4 weeks after birth. About 53% of the patches contained BKCa channels in the normoxic group, but only 20% in the hypoxic one. There were no differences in channel conductance or reversal potential between the groups. Yet, the open probability of BKCa channels was much less in hypoxic neurons than that in the control, because of a decrease in channel open time and a prolongation of the closed time. These were partially recovered by an oxidizing but not by reducing agent, suggesting an involvement of redox mechanism. Results indicate that the Ca2+-activated K+ channel activities in hippocampal CA1 neurons are modulated by hypoxia during maturation. The reduction in BKCa activity may contribute to hypoxia-induced neuronal hyperexcitability. © 2002 Elsevier Science Ireland Ltd. All rights reserved.