Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/ EPM), Rua Botucatu 862, 1° andar, Vila Clementino, São Paulo, SP 04023-062, Brazil.
Curr Mol Pharmacol. 2016;9(4):332-336. doi: 10.2174/1874467209666160408152558.
Epilepsy is one of the most prevalent neurological disorders worldwide, but its underlying mechanisms have not yet been clarified. Among the possible molecular mechanisms that underlie its occurrence are those that are responsible for the neuronal ionic gradient, including the transmembrane enzyme Na+,K+;-adenosine triphosphatase (ATPase). Na+,K+-ATPase plays an important role in controlling neuronal excitability, and it is believed to be related to the pathophysiology of epilepsy. However, the specific isozymes that may be related to this neurological disorder remain to be determined. The α3 subunit-containing Na+,K+-ATPase isozyme has high affinity for ouabain and appears to play a major role in the pathogenesis of epilepsies. However, more studies are needed to evaluate the possible participation of Na+,K+- ATPase isozymes with lower affinity for ouabain (i.e., those that contain the α1 and α2 subunits).
The present study investigated whether rats with high (HTR) and low (LTR) thresholds for clonic convulsions that are induced by a benzodiazepine inverse agonist differ in the binding of [3;H]- ouabain to Na+,K+-ATPase isozymes with lower affinity to ouabain in discrete brain regions.
Compared with the HTR group, the LTR group exhibited lower binding of [3H]-ouabain in the brainstem and frontal cortex.
This finding supports the hypothesis that epilepsy is associated with impairments in Na+,K+- ATPase activity. The results also suggest that Na+,K+;-ATPase isozymes that contain the α1/α2 subunits in these brain regions may underlie the susceptibility to methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate-induced convulsions.
癫痫是全球最常见的神经障碍之一，但发病机制尚未阐明。在可能导致其发生的分子机制中，有负责神经元离子梯度的机制，包括跨膜酶 Na+，K+-三磷酸腺苷酶（ATPase）。Na+，K+-ATPase 在控制神经元兴奋性方面发挥着重要作用，并且被认为与癫痫的病理生理学有关。但是，与这种神经障碍相关的具体同工酶仍有待确定。含α3 亚基的 Na+，K+-ATPase 同工酶对哇巴因具有高亲和力，并且似乎在癫痫发病机制中起主要作用。但是，需要更多的研究来评估与哇巴因亲和力较低的 Na+，K+-ATPase 同工酶（即包含α1 和α2 亚基的同工酶）的可能参与。
本研究探讨了由苯二氮䓬反向激动剂诱导的具有高（HTR）和低（LTR）阵挛性惊厥阈值的大鼠在离散脑区中与哇巴因亲和力较低的 Na+，K+-ATPase 同工酶的[3H]-哇巴因结合是否存在差异。
与 HTR 组相比，LTR 组在脑干和额叶皮质中[3H]-哇巴因的结合减少。
这一发现支持了癫痫与 Na+，K+-ATPase 活性受损有关的假说。结果还表明，这些脑区中含有α1/α2 亚基的 Na+，K+-ATPase 同工酶可能是甲基 6,7-二甲氧基-4-乙基-β-咔啉-3-羧酸酯诱导的惊厥易感性的基础。
