Deficiency of Thyroid Hormone Reduces Voltage-Gated Na+ Currents as Well as Expression of Na+/K+-ATPase in the Mouse Hippocampus

Abstract

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 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.

Hormonal Changes in Women with Epilepsy

“…The elucidation of the mechanism by which THs influence susceptibility to seizures in the brain remains necessary. It has been confirmed that elevated levels of THs can modify the function of sodium-potassium adenosine triphosphatase, thereby leading to changes in neuronal sodium concentrations, 11 ultimately resulting in a reduction of the seizure threshold. In contrast, the administration of TRH directly into the hippocampus demonstrated anticonvulsant properties in rats with amygdala-kindled seizures, as evidenced by a reduction in after-discharge duration and seizure duration.…”