Phasic GABAA -receptor activation is required to suppress epileptiform activity in the CA3 region of the immature rat hippocampus
| Autor: | Sergey N, Kolbaev, Salim, Sharopov, Paul W, Dierkes, Heiko J, Luhmann, Werner, Kilb |
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| Rok vydání: | 2012 |
| Předmět: |
Patch-Clamp Techniques
Age Factors Action Potentials Convulsants Tetrodotoxin In Vitro Techniques Receptors GABA-A CA3 Region Hippocampal Biophysical Phenomena Electric Stimulation Rats GABA Antagonists Pyridazines Animals Newborn Inhibitory Postsynaptic Potentials Animals Picrotoxin Rats Wistar gamma-Aminobutyric Acid Sodium Channel Blockers |
| Zdroj: | Epilepsia. 53(5) |
| ISSN: | 1528-1167 |
| Popis: | Despite the consistent observation that γ-aminobutyric acid A (GABA(A) ) receptors mediate excitatory responses at perinatal stages, the role of the GABAergic system in the generation of neonatal epileptiform activity remains controversial. Therefore, we analyzed whether tonic and phasic GABAergic transmission had differential effects on neuronal excitability during early development. We performed whole cell patch-clamp and field potential recordings in the CA3 region of hippocampal slices from immature (postnatal day 4-7) rats to analyze the effect of specific antagonists and modulators of tonic and phasic GABAergic components on neuronal excitability. The GABAergic antagonists gabazine (3 μm) and picrotoxin (100 μm) induced epileptiform discharges, whereas activation of GABA(A) receptors attenuated epileptiform discharges. Under low-Mg(2+) conditions, 100 nm gabazine and 1 μm picrotoxin were sufficient to provoke epileptiform activity in 63.2% (n = 19) and 53.8% (n = 26) of the slices, respectively. Whole-cell patch-clamp experiments revealed that these concentrations significantly reduced the amplitude of phasic GABAergic postsynaptic currents but had no effect on tonic currents. In contrast, 1-μm 4,5,6,7-tetrahydroisoxaz-olo[5,4-c]-pyridin-3-ol (THIP) induced a tonic current of -12 ± 2.5 pA (n = 6) and provoked epileptiform discharges in 57% (n = 21) of the slices. We conclude from these results that in the early postnatal rat hippocampus a constant phasic synaptic activity is required to control excitability and prevent epileptiform activity, whereas tonic GABAergic currents can mediate excitatory responses. Pharmacologic intervention at comparable human developmental stages should consider these ambivalent GABAergic actions. |
| Databáze: | OpenAIRE |
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