Regional Distributions of Hippocampal Na⁺, K⁺‐ATPase, Cytochrome Oxidase, and Total Protein in Temporal Lobe Epilepsy

Abstract

Na+,K(+)-ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+,K(+)-ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie-stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump density/unit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.

Hippocampal gene expression dysregulation of Klotho, nuclear factor kappa B and tumor necrosis factor in temporal lobe epilepsy patients

“…Considering the importance of Na + /K + ATPase activity in neuronal electrical activity and excitability [24], it is important to determine if KL regulates Na + /K + ATPase in the hippocampus, which could be involved with the evident synaptic reduction found in Kl −/− mice [6,7]. The molecular mechanisms regarding the neurodegenerative feature found in Kl −/− mice and analogously to HS have not yet been elucidated.…”

Temporal and topographic alterations in expression of the α3 isoform of Na+,K+-ATPase in the rat freeze lesion model of microgyria and epileptogenesis

“…Both decreases and increases in pump activity have been found in animal models of epilepsy (Cowan and Cavalheiro, 1980; Anderson et al, 1994; Kang et al, 2004) and in human epileptic brain (Brines et al, 1995), suggesting that both epileptogenic lesions and abnormal activity itself can influence expression of the pump.…”

Implication of Kir4.1 Channel in Excess Potassium Clearance: AnIn VivoStudy on Anesthetized Glial-Conditional Kir4.1 Knock-Out Mice

“…One could also speculate that a more intense ATPase activity would lead to a longer recovery to baseline and that the compensatory mechanisms for K ir depletion may rely on the ATPase. In epileptic tissue, K ir conductance, as well as ATPase activity, are decreased (Brines et al, 1995;Vaillend et al, 2002). This combination of factors could contribute to the observed impaired [K ϩ ] o homeostasis.…”