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S.M. Sundaram, R. Marx, H.M. Lesslich, and I.D. Dietzel (2022).
Deficiency of thyroid hormone reduces voltage-gated Na⁺ currents as well as expression of Na⁺/K⁺-ATPase in the mouse hippocampus.
International Journal of Molecular Sciences 23: 4133
doi: 10.3390/ijms23084133

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 fromPax8^–/– mice. Pax8^–/– mice also showed significantly decreased protein expression levels of the catalytic α1 and α3 subunits of the Na⁺/K⁺-ATPase as well as decreased levels of the β2 isoform, with no changes in the α2 and β1 subunits.