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Progesterone blocks multiple routes of ion flux

Brooke G Kelley1, Paul G Mermelstein

  • 1Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.

Molecular and Cellular Neurosciences
|July 26, 2011
PubMed

Insights

Progesterone shows neuroprotective effects by blocking multiple ion channels in neurons, independent of its nuclear receptor. This action may offer new therapeutic avenues for brain injury but also suggests potential side effects.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cellular Biology

Background:

  • Progesterone is being investigated as a neuroprotective agent for traumatic brain injury (TBI).
  • Previous research indicated progesterone inhibits excitotoxicity by blocking voltage-gated calcium channels, independent of the progesterone receptor.

Purpose of the Study:

  • To investigate the effects of therapeutic progesterone concentrations on other neuronal ion channels and currents.
  • To elucidate the mechanism of progesterone's neuroprotective action.

Main Methods:

  • Cultured rat striatal neurons were used to study the effects of progesterone.
  • Electrophysiological techniques were employed to assess ion channel and neurotransmitter receptor function.

Main Results:

  • Progesterone blocked voltage-gated potassium channels, sodium channels, and GABA(A) currents at therapeutic concentrations.
  • These actions were steroid-specific, voltage-independent, and concentration-dependent, occurring at the neuronal surface membrane.

Conclusions:

  • Progesterone exhibits broad effects on neuronal ion channels, similar to dihydropyridines.
  • These findings suggest shared mechanisms of action, potential for expanded therapeutic applications, and possible adverse effects of progesterone in TBI treatment.

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