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Electrophysiological characterization of a Cav3.2 calcium channel missense variant associated with epilepsy and hearing loss
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SYSNO ASEP 0576183 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Electrophysiological characterization of a Cav3.2 calcium channel missense variant associated with epilepsy and hearing loss Author(s) Stringer, Robin Nicholas (UOCHB-X)
Cmarko, Leoš (UOCHB-X) ORCID
Zamponi, G. W. (CA)
De Waard, M. (FR)
Weiss, N. (CZ)Article number 68 Source Title Molecular Brain. - : BioMed Central - ISSN 1756-6606
Roč. 16, č. 1 (2023)Number of pages 5 s. Language eng - English Country GB - United Kingdom Keywords Cav3.2 ; CACNA1H ; calcium channels ; channelopathy ; epilepsy ; hearing ; ion channels ; mutation ; T-type channels OECD category Biochemistry and molecular biology R&D Projects LX22NPO5104 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 001070896600001 EID SCOPUS 85171856530 DOI https://doi.org/10.1186/s13041-023-01058-2 Annotation T-type calcium channelopathies encompass a group of human disorders either caused or exacerbated by mutations in the genes encoding different T-type calcium channels. Recently, a new heterozygous missense mutation in the CACNA1H gene that encodes the Cav3.2 T-type calcium channel was reported in a patient presenting with epilepsy and hearing loss—apparently the first CACNA1H mutation to be associated with a sensorineural hearing condition. This mutation leads to the substitution of an arginine at position 132 with a histidine (R132H) in the proximal extracellular end of the second transmembrane helix of Cav3.2. In this study, we report the electrophysiological characterization of this new variant using whole-cell patch clamp recordings in tsA-201 cells. Our data reveal minor gating alterations of the channel evidenced by a mild increase of the T-type current density and slower recovery from inactivation, as well as an enhanced sensitivity of the channel to external pH change. To what extend these biophysical changes and pH sensitivity alterations induced by the R132H mutation contribute to the observed pathogenicity remains an open question that will necessitate the analysis of additional CACNA1H variants associated with the same pathologies. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.1186/s13041-023-01058-2
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