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Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells

Jin-Ho Song1, Jay Z Yeh

  • 1Department of Pharmacology, College of Medicine, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 156-756, Republic of Korea. jinhos@cau.ac.kr

Neuroscience Letters
|April 11, 2012
PubMed

Insights

Dextromethorphan, a cough medicine, was found to inhibit microglial proton currents. This action may suppress microglial activation and offer neuroprotection.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Dextromethorphan exhibits neuroprotective effects by reducing pro-inflammatory cytokines and reactive oxygen species from microglia.
  • Microglial activation relies on NADPH oxidase, which is supported by voltage-gated proton channels that manage intracellular acid buildup.

Purpose of the Study:

  • To investigate the impact of dextromethorphan on proton currents in microglial BV2 cells.
  • To determine if dextromethorphan's neuroprotective properties are linked to its effect on microglial proton channels.

Main Methods:

  • Utilized microglial BV2 cells to study proton currents.
  • Applied dextromethorphan and measured its inhibitory effects on proton currents using electrophysiology.
  • Assessed the IC(50) value and effects on reversal potential and voltage dependence.
  • Tested major dextromethorphan metabolites for inhibitory activity.

Main Results:

  • Dextromethorphan demonstrated reversible inhibition of proton currents in microglial BV2 cells.
  • The calculated IC(50) for dextromethorphan was 51.7 μM under specific pH conditions.
  • Neither dextrorphan, 3-hydroxymorphinan, nor dextromethorphan methiodide showed significant inhibition.
  • Dextromethorphan did not alter the reversal potential or voltage-dependent gating of the proton channels.

Conclusions:

  • Dextromethorphan effectively inhibits microglial voltage-gated proton channels.
  • This inhibition is likely responsible for suppressing NADPH oxidase activity and subsequent microglial activation.
  • The findings suggest a mechanism for dextromethorphan's neuroprotective actions.

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