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

• Published in: Neuroscience letters 2012-05, Vol.516 (1), p.94-98
• Main Authors: Song, Jin-Ho, Yeh, Jay Z.
• Format: Article
• Language: English
• Subjects: 3-Hydroxymorphinan; Animals; Antitussive Agents - administration & dosage; Cell Line; Channel gating; Cytokines; Dextromethorphan; Dextromethorphan - administration & dosage; Dextrorphan; Dose-Response Relationship, Drug; Drugs; Inflammation; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Ion Channels - antagonists & inhibitors; Ion Channels - metabolism; Metabolites; Mice; Microglia; Microglia - drug effects; Microglia - physiology; Microglial BV2 cell; Microglial cells; NAD(P)H oxidase; Nervous system; Neuroprotection; pH effects; Protons; Reactive oxygen species; Voltage-gated proton channel
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2012.03.065

► Dextromethorphan inhibits voltage-gated proton currents in BV2 microglial cells. ► Dextromethorphan does not change the reversal potential. ► Dextromethorphan does not change the voltage dependence of the gating. ► Dextrorphan and 3-hydroxymorphinan are ineffective to inhibit proton currents. ► Dextromethorphan methiodide is ineffective to inhibit proton currents. 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 IC50 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.