Peroxynitrite alters GABAergic synaptic transmission in immature rat hippocampal slices.
Increasing of peroxynitrite (ONOO(-)) production during ischemia in the immature brain was considered to be associated with impaired cognitive function. GABAergic synapses played an important role in memory formation including the induction of long-term potentiation (LTP) and long-term depression (LTD) in hippocampus. In the present study, we examined the effects of acute exposure of the ONOO(-) donor, SIN-1 on GABAergic synaptic transmission in immature rat hippocampal slices with whole-cell patch-clamp recordings. The results showed that SIN-1 increased the peak amplitude of evoked inhibitory postsynaptic currents (eIPSCs) and decreased paired pulse ratio via the formation of ONOO(-). In addition, it also increased the frequency of spontaneous (but not miniature) IPSCs in a dose-dependent manner without altering amplitudes or rise and decay times of both (sIPSCs and mIPSCs). It further demonstrated that the presynaptic action of SIN-1 was external calcium dependent and was not related to the changes of interneuron excitability. This study provides electrophysiological evidences from developing hippocampal slices to support that SIN-1 enhances action potential-dependent GABA release. It suggests that the potentiation effect of ONOO(-) may contribute to hyperexcitability and seizures and may underlie one of the mechanisms by which ischemia increases seizure susceptibility in the immature brain.
College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Jiajia
J
Yang
Zhaowei
Z
Liu
Yongling
Y
Xie
Zhuo
Z
Yang
Tao
T
Zhang
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects; D008981:Molsidomine / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D020030:Nitric Oxide Donors; D030421:Peroxynitrous Acid; D005680:gamma-Aminobutyric Acid; D008981:Molsidomine