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Sivaraj Mohana Sundaram, Romy Marx, Heiko M. Lesslich, Irmgard D. Dietzel-Meyer

• 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.