Guillaume D
Department of Neurology, University of Liège, Belgium.
Acta Neurol Belg. 1988 Nov-Dec;88(5):257-80.
(Na+, K+)-ATPase (E.C.3.6.1.3) was partially purified from the cerebral cortex of audiogenic DBA/2 mice, from the primary and secondary epileptogenic foci of cats with a freeze lesion and from normal and epileptic human cortices. No differences in the specific activities of the microsomal enzyme were observed between normal and epileptic cortex. The influence of K+ ions and phenytoin, a potent antiepileptic drug, was then studied on the phosphorylation level of (Na+, K+)-ATPase alpha(+) (neuronal) and alpha(-) (non-neuronal) catalytic subunits resolved by SDS-gel electrophoresis. In normal cortex, the apparent affinity of the non-neuronal enzyme to K+ ions was reduced compared to the affinity of the neuronal enzyme. Phenytoin decreased the phosphorylation level of (Na+, K+)-ATPase purified from non-epileptogenic cortex of control C57/BL mice, cats and human patients. In fact, the drug induced the dephosphorylation of the (Na+, K+)-ATPase catalytic subunits, mainly of its alpha(-), non-neuronal subtype. In the cortex of audiogenic DBA/2 mice, K+ ions induced the dephosphorylation of (Na+, K+)-ATPase, with the same affinity as in control C57/BL mice. The dephosphorylating influence of phenytoin was however much decreased. In the primary and secondary foci of lesioned cats, both K+ and phenytoin dephosphorylating influences were decreased. Those changes were especially valid for the alpha(-), non-neuronal subunit. In human epileptic cortex, the (Na+, K+)-ATPase catalytic subunit had a decreased affinity to K+, as well as it lost its sensitivity to phenytoin dephosphorylation. Those results confirm the existence of two molecular forms of (Na+, K+)-ATPase in animal and human brain cortex. Those two forms, the neuronal and the non-neuronal or glial (Na+, K+)-ATPases, differ at least by their K+ regulation and their phenytoin sensitivity. Phenytoin studies also suggest that the drug stimulates the cortical (Na+, K+)-ATPase, mainly its glial form, providing central nervous system with an enhanced ability to regulate extracellular K+. In epileptic cortex, (Na+, K+)-ATPase and especially its glial form is altered in its K+ regulation and phenytoin sensitivity. That deficiency of glial (Na+, K+)-ATPase in focal epileptogenic cortex could be responsible for ictal transformation and seizure spread (Acta neurol. belg., 1988, 88, 257-280).
（钠钾）-ATP酶（E.C.3.6.1.3）从听源性DBA/2小鼠的大脑皮层、有冷冻损伤的猫的原发性和继发性致痫灶以及正常和癫痫患者的大脑皮层中部分纯化得到。在正常和癫痫皮层之间未观察到微粒体酶比活性的差异。随后研究了钾离子和苯妥英（一种强效抗癫痫药物）对通过SDS-凝胶电泳分离的（钠钾）-ATP酶α（+）（神经元型）和α（-）（非神经元型）催化亚基磷酸化水平的影响。在正常皮层中，非神经元型酶对钾离子的表观亲和力低于神经元型酶。苯妥英降低了从对照C57/BL小鼠、猫和人类患者的非致痫皮层中纯化得到的（钠钾）-ATP酶的磷酸化水平。实际上，该药物诱导了（钠钾）-ATP酶催化亚基的去磷酸化，主要是其α（-）非神经元亚型。在听源性DBA/2小鼠的皮层中，钾离子诱导了（钠钾）-ATP酶的去磷酸化，其亲和力与对照C57/BL小鼠相同。然而，苯妥英的去磷酸化作用大大降低。在损伤猫的原发性和继发性病灶中，钾离子和苯妥英的去磷酸化作用均降低。这些变化对α（-）非神经元亚基尤为明显。在人类癫痫皮层中，（钠钾）-ATP酶催化亚基对钾离子的亲和力降低，并且失去了对苯妥英去磷酸化的敏感性。这些结果证实了在动物和人类大脑皮层中存在两种（钠钾）-ATP酶分子形式。这两种形式，即神经元型和非神经元型或胶质（钠钾）-ATP酶，至少在钾离子调节和对苯妥英的敏感性方面存在差异。对苯妥英的研究还表明，该药物刺激皮层（钠钾）-ATP酶，主要是其胶质形式，从而增强中枢神经系统调节细胞外钾离子的能力。在癫痫皮层中，（钠钾）-ATP酶，尤其是其胶质形式，在钾离子调节和对苯妥英的敏感性方面发生了改变。局灶性致痫皮层中胶质（钠钾）-ATP酶的这种缺陷可能是发作转化和癫痫扩散的原因（《比利时神经学学报》，1988年，88卷，257 - 280页）。
