Neurosteroids block Ca2+ channel current in freshly isolated hippocampal CA1 neurons.
Certain synthetic and endogenous steroids are known to modulate neuronal responses to gamma-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 microM) 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 microM). Tail current analysis shows that THCC appears to be a ligand that selectively and reversibly depresses the omega-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.
Ffrench-Mullen
J M
JM
Department of Pharmacology, ICI Pharmaceuticals Group, ICI Americas Inc., Wilmington, DE 19897.
Spence
K T
KT
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009420:Nervous System / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000302:isolation & purification / Q000494:pharmacology*; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D003687:Dehydroepiandrosterone; D010456:Peptides, Cyclic; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013256:Steroids; D013739:Testosterone; D020866:omega-Conotoxin GVIA; C068233:testosterone-3-(n-hexyl)cyclobutane carboxylate