Deficiency of thyroid hormone reduces voltage-gated \(Na^{+}\) currents as well as expression of \(Na^{+}/K^{+}\)-ATPase in the mouse hippocampus
- Mice lacking functional thyroid follicular cells, \(\it Pax8^{−/−}\) mice, die early postnatally, making them suitable models for extreme hypothyroidism. We have previously obtained evidence in postnatal rat neurons, that a down-regulation of \(Na^{+}\)-current density could explain the reduced excitability of the nervous system in hypothyroidism. If such a mechanism underlies the development of coma and death in severe hypothyroidism, \(\it Pax8^{−/−}\) mice should show deficits in the expression of \(Na^{+}\) currents and potentially also in the expression of \(Na^{+}/K^{+}\)-ATPases, which are necessary to maintain low intracellular \(Na^{+}\) levels. We thus compared \(Na^{+}\) current densities in postnatal mice using the patch-clamp technique in the whole-cell configuration as well as the expression of three alpha and two beta-subunits of the \(Na^{+}/K^{+}\)-ATPase in wild type versus \(\it Pax8^{−/−}\) mice. Whereas the \(Na^{+}\) current density in hippocampal neurons from wild type mice was upregulated within the first postnatal week, the \(Na^{+}\) current density remained at a very low level in hippocampal neurons from \(\it Pax8^{−/−}\) mice. \(\it Pax8^{−/−}\) mice also showed significantly decreased protein expression levels of the catalytic \(\alpha\)1 and \(\alpha\)3 subunits of the \(Na^{+}/K^{+}\)-ATPase as well as decreased levels of the \(\beta\)2 isoform, with no changes in the \(\alpha\)2 and \(\beta\)1 subunits.
Author: | Sivaraj Mohana SundaramGND, Romy MarxGND, Heiko M. LesslichORCiDGND, Irmgard D. Dietzel-MeyerORCiDGND |
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URN: | urn:nbn:de:hbz:294-92294 |
DOI: | https://doi.org/10.3390/ijms23084133 |
Parent Title (English): | International journal of molecular sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/08/15 |
Date of first Publication: | 2022/04/08 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds \(Na^{+}/K^{+}\) -ATPase; \(Na^{+}\) current density; congenital hypothyroidism; hippocampal neurons; mouse brain; thyroid hormone; triiodo-L-thyronine |
Volume: | 23 |
Issue: | 8, Article 4133 |
First Page: | 4133-1 |
Last Page: | 4133-14 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Lehrstuhl Biochemie II, Arbeitsgruppe Elektrobiochemie neuraler Zellen |
Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Chemie, Kristallographie, Mineralogie |
open_access (DINI-Set): | open_access |
faculties: | Fakultät für Chemie und Biochemie |
International Graduate School of Neuroscience (IGSN) | |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |