Neurosteroids block Ca²⁺ channel current in freshly isolated hippocampal CA1 neurons

Abstract

Certain synthetic and endogenous steroids are known to modulate neuronal responses to -γ-aminobutyric acid (GABA) and also change the firing frequency of certain neurons. However, there is nothing known of the effect(s) of steroids on voltage-gated calcium currents in mammalian neurons. We show here that the steroids (0.1–100 μM) allotetrahydrocorticosterone (THCC), dehydroepiandrosterone sulfate (DHEAS) and pregnanolone can rapidly and reversibly depress voltage-gated calcium currents in freshly isolated adult hippocampal CA1 pyramidal neurons. This blocking action occurs in the presence of picrotoxin (10 μM). Tail current analysis shows that THCC appears to be a ligand that selectively and reversibly depresses the ω-conotoxin (fraction GVIA) sensitive portion of the calcium current. These results demonstrate that certain steroid metabolites have a direct membrane site of action which may influence brain excitability.