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Activation of glycine receptors modulates spontaneous epileptiform activity in the immature rat hippocampus
Author(s) -
Chen Rongqing,
Okabe Akihito,
Sun Haiyan,
Sharopov Salim,
HanganuOpatz Ileana L.,
Kolbaev Sergei N.,
Fukuda Atsuo,
Luhmann Heiko J.,
Kilb Werner
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.271700
Subject(s) - strychnine , glycine receptor , glycine , gabaa receptor , receptor , chemistry , hippocampus , taurine , pharmacology , neuroscience , biochemistry , biology , amino acid
Key points Taurine has a pro‐ and anticonvulsive effect on the immature hippocampus, depending on the dose. The taurine effect is mediated by GABA A and glycine receptors. The taurine effect can be partially mimicked by glycine. Inhibition of glycine receptors has a weak proconvulsive effect on the immature hippocampus. We conclude that an endogenous activation of glycine receptors by glycine or taurine contributed to the control of neuronal excitability in the immature hippocampus.Abstract While the expression of glycine receptors in the immature hippocampus has been shown, no information about the role of glycine receptors in controlling the excitability in the immature CNS is available. Therefore, we examined the effect of glycinergic agonists and antagonists in the CA3 region of an intact corticohippocampal preparation of the immature (postnatal days 4–7) rat using field potential recordings. Bath application of 100 μ m taurine or 10 μ m glycine enhanced the occurrence of recurrent epileptiform activity induced by 20 μ m 4‐aminopyridine in low Mg 2+ solution. This proconvulsive effect was prevented by 3 μ m strychnine or after incubation with the loop diuretic bumetanide (10 μ m ), suggesting that it required glycine receptors and an active NKCC1‐dependent Cl − accumulation. Application of higher doses of taurine (≥1 m m ) or glycine (100 μ m ) attenuated recurrent epileptiform discharges. The anticonvulsive effect of taurine was also observed in the presence of the GABA A receptor antagonist gabazine and was attenuated by strychnine, suggesting that it was partially mediated by glycine receptors. Bath application of the glycinergic antagonist strychnine (0.3 μ m ) induced epileptiform discharges. We conclude from these results that in the immature hippocampus, activation of glycine receptors can mediate both pro‐ and anticonvulsive effects, but that a persistent activation of glycine receptors is required to suppress epileptiform activity. In summary, our study elucidated the important role of glycine receptors in the control of neuronal excitability in the immature hippocampus.