Distinct effects between dehydroepiandrosterone and its sulfate ester on voltage-gated sodium channels

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are neurosteroids which are synthesized in the brain. We investigated the effects of these steroids on carecholamine (CA) secretion and Na+ influx in bovine adrenal chromaffin cells, a model of a catecholaminergic neuron, evoked by veratridine, which is an activator of voltage-gated Na+ channels. DHEAS (3-100 μM) enhanced the veratridine-evoked CA secretion and at 300 μM had no effect on it. However, DHEAS did not affect the secretion by 56 mM K+, which activates voltage-gated Ca2+ channels. The enhancement effect of DHEAS was not affected by ouabain, a Na/K-ATPase inhibitor. DHEAS shifted leftward the concentration-response curve for veratridine-evoked secretion. The steroid also potentiated the veratridine-induced Na+ influx. On the other hand, DHEA (30-300 μM) similarly inhibited both the veratridine- and 56 mM K+-induced CA secretions. DHEA also inhibited the veratridine-induced Na+ influx. These results indicate that DHEA and DHEAS may modulate the voltage-gated Na+ channel-mediated response via the adverse effects.