Dissecting the Molecular Determinants of GABA(A) Receptors Current Rundown, a Hallmark of Refractory Human Epilepsy.
Dissecting the Molecular Determinants of GABA(A) Receptors Current Rundown, a Hallmark of Refractory Human Epilepsy.
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剖析 GABA(A) 受体电流表的分子决定因素，这是难治性人类癫痫的标志。
DOI：
10.3390/brainsci11040441
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发表时间：
2021-03-30
期刊：
影响因子：
3.3
通讯作者：
Palma E
中科院分区：
文献类型：
--
作者：
Cifelli P;Di Angelantonio S;Alfano V;Morano A;De Felice E;Aronica E;Ruffolo G;Palma E
GABAA receptors-(Rs) are fundamental for the maintenance of an efficient inhibitory function in the central nervous system (CNS). Their dysfunction is associated with a wide range of CNS disorders, many of which characterized by seizures and epilepsy. Recently, an increased use-dependent desensitization due to a repetitive GABA stimulation (GABAA current rundown) of GABAARs has been associated with drug-resistant temporal lobe epilepsy (TLE). Here, we aimed to investigate the molecular determinants of GABAA current rundown with two different heterologous expression systems (Xenopus oocytes and human embryonic kidney cells; HEK) which allowed us to manipulate receptor stoichiometry and to study the GABAA current rundown on different GABAAR configurations. To this purpose, we performed electrophysiology experiments using two-electrode voltage clamp in oocytes and confirming part of our results in HEK. We found that different degrees of GABAA current rundown can be associated with the expression of different GABAAR β-subunits reaching the maximum current decrease when functional α1β2 receptors are expressed. Furthermore, the blockade of phosphatases can prevent the current rundown observed in α1β2 GABAARs. Since GABAAR represents one important therapeutic target in the treatment of human epilepsy, our results could open new perspectives on the therapeutic management of drug-resistant patients showing a GABAergic impairment.
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DOI：
10.1073/pnas.0710522105
发表时间：
2007-12-26
影响因子：
11.1
作者：
Palma, Eleonora;Roseti, Cristina;Eusebi, Fabrizio
通讯作者：
Eusebi, Fabrizio
影响因子：
4.8
作者：
Brandon, NJ;Delmas, P;Moss, SJ
通讯作者：
Moss, SJ
DOI：
10.1073/pnas.0438006100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Palma, E;Trettel, F;Eusebi, F
通讯作者：
Eusebi, F
影响因子：
5.3
作者：
Loup, F;Wieser, HG;Fritschy, JM
通讯作者：
Fritschy, JM
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.