In:
Journal of Neurophysiology, American Physiological Society, Vol. 110, No. 1 ( 2013-07-01), p. 95-102
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 (GABA A ) 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 GABA A 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 GABA A 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 GABA A 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.
Type of Medium:
Online Resource
ISSN:
0022-3077
,
1522-1598
DOI:
10.1152/jn.00727.2012
RVK:
XA 10000 ; XA 552555
Language:
English
Publisher:
American Physiological Society
Publication Date:
2013
detail.hit.zdb_id:
80161-6
detail.hit.zdb_id:
1467889-5
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