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

Sheilabi, Mariam A, Takeshita, Louise Y ORCID: 0000-0003-4288-4388, Sims, Edward J, Falciani, Francesco ORCID: 0000-0003-1432-2871 and Princivalle, Alessandra P (2020) The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (8). E2955-.

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Official URL: http://dx.doi.org/10.3390/ijms21082955

Abstract

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 SCN4B 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 SCN4B we then discovered a linkage between the expression of this gene and K+ channels activated by Ca2+, or K+ two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of SCN4B. These observations support the hypothesis that SCN4B 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.

Item Type:	Article
Uncontrolled Keywords:	temporal lobe epilepsy, hippocampal sclerosis, antiepileptic drug resistance, SCN4B, voltage-gated sodium channels, Nav beta 4 subunit
Depositing User:	Symplectic Admin
Date Deposited:	24 Apr 2020 14:57
Last Modified:	25 Jan 2024 12:36
DOI:	10.3390/ijms21082955
Open Access URL:	https://www.mdpi.com/1422-0067/21/8/2955/pdf
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3084430