The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
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...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Mariam A. Sheilabi Louise Y. Takeshita Edward J. Sims Francesco Falciani Alessandra P. Princivalle |
| author_facet | Mariam A. Sheilabi Louise Y. Takeshita Edward J. Sims Francesco Falciani Alessandra P. Princivalle |
| author_sort | Mariam A. Sheilabi |
| collection | DOAJ |
| description | 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 <i>SCN4B</i> 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 <i>SCN4B</i> we then discovered a linkage between the expression of this gene and K<sup>+</sup> channels activated by Ca<sup>2+</sup>, or K<sup>+</sup> two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of <i>SCN4B</i>. These observations support the hypothesis that <i>SCN4B</i> 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. |
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| last_indexed | 2024-03-10T20:18:43Z |
| publishDate | 2020-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bfe2ee8879494d369b9463bac03bbb372023-11-19T22:24:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218295510.3390/ijms21082955The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant PatientsMariam A. Sheilabi0Louise Y. Takeshita1Edward J. Sims2Francesco Falciani3Alessandra P. Princivalle4Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKInstitute of Integrative Biology, University of Liverpool, Biosciences Building, Liverpool L69 7ZB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKInstitute of Integrative Biology, University of Liverpool, Biosciences Building, Liverpool L69 7ZB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKTemporal 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 <i>SCN4B</i> 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 <i>SCN4B</i> we then discovered a linkage between the expression of this gene and K<sup>+</sup> channels activated by Ca<sup>2+</sup>, or K<sup>+</sup> two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of <i>SCN4B</i>. These observations support the hypothesis that <i>SCN4B</i> 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.https://www.mdpi.com/1422-0067/21/8/2955temporal lobe epilepsyhippocampal sclerosisantiepileptic drug resistance<i>SCN4B</i>voltage-gated sodium channelsNav β4 subunit |
| spellingShingle | Mariam A. Sheilabi Louise Y. Takeshita Edward J. Sims Francesco Falciani Alessandra P. Princivalle The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients International Journal of Molecular Sciences temporal lobe epilepsy hippocampal sclerosis antiepileptic drug resistance <i>SCN4B</i> voltage-gated sodium channels Nav β4 subunit |
| title | The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients |
| title_full | The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients |
| title_fullStr | The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients |
| title_full_unstemmed | The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients |
| title_short | The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients |
| title_sort | sodium channel b4 subunits are dysregulated in temporal lobe epilepsy drug resistant patients |
| topic | temporal lobe epilepsy hippocampal sclerosis antiepileptic drug resistance <i>SCN4B</i> voltage-gated sodium channels Nav β4 subunit |
| url | https://www.mdpi.com/1422-0067/21/8/2955 |
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