The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients

• Published in: International journal of molecular sciences 2020-04, Vol.21 (8), p.2955
• Main Authors: Sheilabi, Mariam A, Takeshita, Louise Y, Sims, Edward J, Falciani, Francesco, Princivalle, Alessandra P
• Format: Article
• Language: English
• Subjects: Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antiepileptic agents; antiepileptic drug resistance; Bioinformatics; Calcium channels; Calcium ions; Cell adhesion & migration; Channels; Computational Biology - methods; Domains; Drug resistance; Drug Resistance - genetics; Epilepsy; Epilepsy, Temporal Lobe - drug therapy; Epilepsy, Temporal Lobe - etiology; Epilepsy, Temporal Lobe - metabolism; Epilepsy, Temporal Lobe - physiopathology; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; hippocampal sclerosis; Humans; Hypotheses; Metabolism; mRNA; Mutation; Nav β4 subunit; Patients; Pore formation; Protein expression; Proteins; Resistance factors; SCN4B; Sodium; Sodium channels (voltage-gated); Temporal lobe; temporal lobe epilepsy; Transcription, Genetic; Voltage-Gated Sodium Channel beta-4 Subunit - genetics; Voltage-Gated Sodium Channel beta-4 Subunit - metabolism; voltage-gated sodium channels
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082955

Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred for surgery due to antiepileptic drug (AED) resistance. A common molecular target for many of these drugs is the voltage-gated sodium channel (VGSC). The VGSC consists of four domains of pore-forming α-subunits and two auxiliary β-subunits, several of which have been well studied in epileptic conditions. However, despite the β4-subunits' role having been reported in some neurological conditions, there is little research investigating its potential significance in epilepsy. Therefore, the purpose of this work was to assess the role of SCN4β in epilepsy by using a combination of molecular and bioinformatics approaches. We first demonstrated that there was a reduction in the relative expression of in the drug-resistant TLE patients compared to non-epileptic control specimens, both at the mRNA and protein levels. By analyzing a co-expression network in the neighborhood of we then discovered a linkage between the expression of this gene and K channels activated by Ca , or K two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of . These observations support the hypothesis that is a key factor in AED-resistant TLE, which could help direct both the drug selection of TLE treatments and the development of future AEDs.