期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/ijms23084133
关键词
thyroid hormone; congenital hypothyroidism; hippocampal neurons; Na+ current density; Na+; K+-ATPase; mouse brain; triiodo-L-thyronine
资金
- International Graduate School of Neuroscience, Ruhr University, Germany
- Wilhelm & Gunther Esser foundation at the Ruhr University - DFG Open Access Publication Funds of the Ruhr-Universitat Bochum
Mice lacking functional thyroid follicular cells, Pax8(-/-) mice, die early postnatally, making them suitable models for extreme hypothyroidism. We have found that Pax8(-/-) mice show deficits in the expression of Na+ currents and Na+/K+-ATPases, leading to reduced neuronal excitability.
Mice lacking functional thyroid follicular cells, 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, 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 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 Pax8(-/-) mice. 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.
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