| 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
|
| リソース情報 |
| ラット |
NER/Kyo(strainID=26) |
