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.
Bibliographical noteFunding Information:
This research was supported by the National Institutes of Health NS41302 (PGM), Core Funding NS062158 , and an IRACDA Post-Doctoral Fellowship GM074628 (BGK). We thank Dr. John Meitzen for his comments on this manuscript.
- Side effects
- Traumatic brain injury