Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.
Summary of "Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells."
Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC(50) value of 51.7μM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation.
Affiliation
Department of Pharmacology, College of Medicine, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 156-756, Republic of Korea.
Journal Details
This article was published in the following journal.
Name: Neuroscience letters
ISSN: 1872-7972
Pages: 94-8
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22487729
- DOI: http://dx.doi.org/10.1016/j.neulet.2012.03.065
Medical and Biotech [MESH] Definitions
Ether-a-go-go Potassium Channels
A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.
Voltage-dependent Anion Channels
A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.
Ion Channel Gating
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
Shaker Superfamily Of Potassium Channels
Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.
Aconitine
A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates voltage-gated SODIUM CHANNELS. It has been used to induce arhythmias in experimental animals and it has antiinflammatory and antineuralgic properties.
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