کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998175 | 1115605 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
1-Ethyl-2-benzimidazolinone (EBIO) suppresses epileptiform activity in in vitro hippocampus
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Ca2+-activated K+ currents with medium (mIAHP) and slow (sIAHP) kinetics, that mediate the post-spike medium and slow after-hyperpolarization (AHP), respectively, play critical roles in regulating neuronal excitability and the spread of epileptiform activity and could provide new therapeutic targets for the management of epileptic patients. We tested if the enhancement of the mIAHP by 1-ethyl-2-benzimidazolinone (EBIO) could suppress epileptiform activity in two in vitro models of epileptogenesis induced in CA3 hippocampal pyramidal neurons by superfusion with 4-AP- and kainate-Mg2+-free solutions. Both interictal- and ictal-like epileptiform activities were reversibly suppressed by EBIO concentrations between 200 μM and 1 mM. EBIO predominantly acted by a strong reduction of excitability via an increase (â450%) of the mIAHP, without changing the sIAHP. Glutamatergic excitatory synaptic transmission was also diminished (â50%) by 1 mM EBIO. In contrast, EBIO concentrations <400 μM had no effect on synaptic excitation, consistent with a lesser sensitivity to the drug than the mIAHP. Apamine (100 nM), a toxin that specifically inhibits the mIAHP, rapidly and reversibly antagonized the blocking effects of EBIO on epileptiform activity. Our results suggest that manipulations that enhance the mIAHP may prove adequate in the treatment of epilepsies; they also suggest that an abnormal down regulation of the mIAHP may be a key factor in the genesis of hyperexcitable states.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 49, Issue 3, September 2005, Pages 376-388
Journal: Neuropharmacology - Volume 49, Issue 3, September 2005, Pages 376-388
نویسندگان
Julieta Garduño, Emilio Galván, David Fernández de Sevilla, Washington Buño,