We have previously shown that treatment with the thyroid hormone triiodo-L-thyronine (T3) 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 T3. The effect of conditioned medium from T3-treated glial cells was mimicked by basic fibroblast growth factor (bFGF), known to be released from cerebellar glial cells after T3-treatment. Neutralisation assays of astrocyte conditioned media (ACM) with anti-bFGF antibody inhibited the regulation of the Nav-D by T3. This suggests that the upregulation of the neuronal sodium current density by T3 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.