Thyroid hormone (T3)-induced up-regulation of voltage-activated sodium current in cultured postnatal hippocampal neurons requires secretion of soluble factors from glial cells.

We have previously shown that treatment with the thyroid hormone T(3) increases the voltage-gated Na(+)current density (Nav-D) in hippocampal neurons from postnatal rats, leading to accelerated action potential upstrokes and increased firing frequencies. Here we show that the Na(+) current regulation depends on the presence of glial cells, which secrete a heat-instable soluble factor upon stimulation with T(3). The effect of conditioned medium from T(3)-treated glial cells was mimicked by basic fibroblast growth factor (bFGF), known to be released from cerebellar glial cells after T(3) treatment. Neutralization assays of astrocyte-conditioned media with anti-bFGF antibody inhibited the regulation of the Nav-D by T(3). This suggests that the up-regulation of the neuronal sodium current density by T(3) is not a direct effect but involves bFGF release and satellite cells. Thus glial cells can modulate neuronal excitability via secretion of paracrinely acting factors.