Relationship Between Susceptibility to DMCM-Induced Generalized Motor Convulsions and Low-Affinity [3H]-Ouabain Binding in Membranes in Rat Brain

Title:Relationship Between Susceptibility to DMCM-Induced Generalized Motor Convulsions and Low-Affinity [3H]-Ouabain Binding in Membranes in Rat Brain

Volume: 9

Author(s): Marcos Brandao Contó and Marco Antonio Campana Venditti

Affiliation:

Keywords: Benzodiazepine inverse agonist, epilepsy, generalized motor convulsions, low-affinity [³H]-ouabain binding, Na⁺, K⁺-ATPase isozymes, ouabain, seizures.

Abstract: Background and Objective: 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).

Methods: 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 [³H]- ouabain to Na⁺,K⁺-ATPase isozymes with lower affinity to ouabain in discrete brain regions.

Results: Compared with the HTR group, the LTR group exhibited lower binding of [³H]-ouabain in the brainstem and frontal cortex.

Conclusion: 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.

Cite this article as:

Contó Brandao Marcos and Venditti Antonio Campana Marco, Relationship Between Susceptibility to DMCM-Induced Generalized Motor Convulsions and Low-Affinity [3H]-Ouabain Binding in Membranes in Rat Brain, Current Molecular Pharmacology 2016; 9 (4) . https://dx.doi.org/10.2174/1874467209666160408152558