title: Progesterone blocks multiple routes of ion flux.
abstract: The administration of progesterone as a neuroprotective agent following traumatic brain injury has recently entered phase III clinical trials. Previous work has demonstrated that therapeutic concentrations of progesterone decrease excitotoxicity through direct inhibition of voltage-gated calcium channels, an action independent of the nuclear progesterone receptor. Here we report using cultured rat striatal neurons that these same concentrations of progesterone also block voltage-gated potassium channels, sodium channels and GABA(A) currents. The actions of progesterone act at the surface membrane of neurons in a steroid specific, voltage-independent, concentration-dependent manner. Notably, these broad actions of progesterone on ion channel and neurotransmitter receptor function mirror those of dihydropyridines, and indicate potential shared mechanisms of action, the prospective of additional therapeutic applications, and possibly, untoward effects.
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.
authors.forename: Brooke G
authors.initials: BG
authors.lastname: Kelley
authors.forename: Paul G
authors.initials: PG
authors.lastname: Mermelstein
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects*; D007477:Ions / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007477:Ions; D024642:Potassium Channels, Voltage-Gated; D011374:Progesterone