Decreased large conductance Ca(2+)-activated K(+) channel activity in dissociated CA1 hippocampal neurons in rats exposed to perinatal and postnatal hypoxia.
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 Ca(2+)-activated K(+) channels in hyperexcitability, we measured large unitary conductance (>200 pS, BK(Ca)) 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 O(2)) for 4 weeks after birth. About 53% of the patches contained BK(Ca) 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 BK(Ca) 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 Ca(2+)-activated K(+) channel activities in hippocampal CA1 neurons are modulated by hypoxia during maturation. The reduction in BK(Ca) activity may contribute to hypoxia-induced neuronal hyperexcitability.
Gao
Tian-Ming
TM
Department of Physiology, The First Military Medical University, Guangzhou, China.
Fung
Man-Lung
ML
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D051662:Kv1.1 Potassium Channel; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C489293:Kcna1 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D004228:Dithionitrobenzoic Acid