論文 - 詳細
| RRC ID | 27723 |
|---|---|
| 著者 | Pandit S, Jeong JA, Jo JY, Cho HS, Kim DW, Kim JM, Ryu PD, Lee SY, Kim HW, Jeon BH, Park JB. |
| タイトル | Dual mechanisms diminishing tonic GABAA inhibition of dentate gyrus granule cells in Noda epileptic rats. |
| ジャーナル | J Neurophysiol |
| Abstract |
The Noda epileptic rat (NER), a Wistar colony mutant, spontaneously has tonic-clonic convulsions with paroxysmal discharges. In the present study, we measured phasic and tonic γ-aminobutyric acid A (GABAA) current (I tonic) in NER hippocampal dentate gyrus granule cells and compared the results with those of normal parent strain Wistar rats (WIS). I tonic, revealed by a bicuculline-induced outward shift in holding current, was significantly smaller in NER than in WIS (P < 0.01). The frequency of inhibitory postsynaptic currents (IPSCs) was also significantly lower in NER than in WIS (P < 0.05), without significant differences in the IPSC amplitude or decay time between WIS and NER. I tonic attenuation in NER was further confirmed in the presence of GABA transporter blockers, NO-711 and nipecotic acid, with no difference in neuronal GABA transporter expression between WIS and NER. I tonic responses to extrasynaptic GABAA receptor agonists (THIP and DS-2) were significantly reduced in NER compared with WIS (P < 0.05). Allopregnanolone caused less I tonic increase in NER than in WIS, while it prolonged the IPSC decay time to a similar rate in the two groups. Expression of the GABAA receptor δ-subunit was decreased in the dentate gyrus of NER relative to that of WIS. Taken together, our results showed that a combination of attenuated presynaptic GABA release and extrasynaptic GABAA receptor expression reduced I tonic amplitude and its sensitivity to neurosteroids, which likely diminishes the gating function of dentate gyrus granule cells and renders NER more susceptible to seizure propagation. |
| 巻・号 | 110(1) |
| ページ | 95-102 |
| 公開日 | 2013-7-1 |
| DOI | 10.1152/jn.00727.2012 |
| PII | jn.00727.2012 |
| PMID | 23576696 |
| MeSH | Animals Dentate Gyrus / physiopathology* Epilepsy, Tonic-Clonic / physiopathology* In Vitro Techniques Male Neural Inhibition / physiology* Rats Rats, Mutant Strains Rats, Wistar Receptors, GABA-A / physiology* |
| IF | 2.234 |
| 引用数 | 13 |
| WOS 分野 | PHYSIOLOGY NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ラット | NER/Kyo(strainID=26) |