Inhibition of the Sodium Calcium Exchanger Suppresses Alcohol Withdrawal-Induced Seizure Susceptibility.
Inhibition of the Sodium Calcium Exchanger Suppresses Alcohol Withdrawal-Induced Seizure Susceptibility.
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DOI：
10.3390/brainsci11020279
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发表时间：
2021-02-23
期刊：
影响因子：
3.3
通讯作者：
N'Gouemo P
中科院分区：
文献类型：
--
作者：
Newton J;Akinfiresoye LR;N'Gouemo P
钙离子内流在癫痫发作的病理生理过程中起着重要作用，包括声诱发的酒精戒断诱发的癫痫发作（AWSs）。一种感兴趣的Ca 2+内流途径是Na+/Ca 2+交换器（NCX），当以其反向模式（NCXrev）活性操作时，其可以促进Ca 2+进入神经元，可能增加神经元兴奋性，从而导致癫痫易感性增强。在这里，我们通过量化SN-6和KB-R7943（分别为亚型1（NCX 1 rev）和3（NCX 3rev）的强效阻断剂）的作用，探讨了NCXrev活性对AWS易感性的影响。使用雄性成年Sprague-Dawley大鼠。声诱发的AWSs由失控性发作（WRSs）演变为全身强直阵挛性发作（GTCS）组成。定量显示，相对低剂量的急性SN-6治疗抑制了AWS的GTCS（但不是WRS）组分的发生，并显著降低了癫痫发作的严重程度。然而，以相对高的剂量施用KB-R7943仅降低GTCS的发生率。这些发现表明，抑制NCX 1 rev活性是抑制酒精戒断诱导的GTCS的假定机制。
Calcium influx plays important roles in the pathophysiology of seizures, including acoustically evoked alcohol withdrawal-induced seizures (AWSs). One Ca2+ influx route of interest is the Na+/Ca2+ exchanger (NCX) that, when operating in its reverse mode (NCXrev) activity, can facilitate Ca2+ entry into neurons, possibly increasing neuronal excitability that leads to enhanced seizure susceptibility. Here, we probed the involvement of NCXrev activity on AWS susceptibility by quantifying the effects of SN-6 and KB-R7943, potent blockers of isoform type 1 (NCX1rev) and 3 (NCX3rev), respectively. Male, adult Sprague–Dawley rats were used. Acoustically evoked AWSs consisted of wild running seizures (WRSs) that evolved into generalized tonic–clonic seizures (GTCSs). Quantification shows that acute SN-6 treatment at a relatively low dose suppressed the occurrence of the GTCSs (but not WRSs) component of AWSs and markedly reduced the seizure severity. However, administration of KB-R7943 at a relatively high dose only reduced the incidence of GTCSs. These findings demonstrate that inhibition of NCX1rev activity is a putative mechanism for the suppression of alcohol withdrawal-induced GTCSs.
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DOI：
10.1196/annals.1387.050
发表时间：
2007-01-01
期刊：
SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE
影响因子：
--
作者：
Annunziato, L.;Pignataro, G.;Di Renzo, G. E.
通讯作者：
Di Renzo, G. E.
影响因子：
--
作者：
Faingold, Carl L
通讯作者：
Faingold, Carl L
影响因子：
2.5
作者：
Papa，M;Canitano，A;Annunziato，L
通讯作者：
Annunziato，L
影响因子：
4.8
作者：
Iwamoto, T;Watano, T;Shigekawa, M
通讯作者：
Shigekawa, M
影响因子：
1.2
作者：
McMicken, David;Liss, Jonathan L.
通讯作者：
Liss, Jonathan L.