Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol.
Autor: | Ghovanloo MR; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA.; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Effraim PR; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA.; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.; Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA., Tyagi S; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA.; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, USA., Zhao P; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA.; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Dib-Hajj SD; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA.; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA., Waxman SG; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA. stephen.waxman@yale.edu.; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA. stephen.waxman@yale.edu.; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA. stephen.waxman@yale.edu. |
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Jazyk: | angličtina |
Zdroj: | Communications biology [Commun Biol] 2024 Jan 23; Vol. 7 (1), pp. 120. Date of Electronic Publication: 2024 Jan 23. |
DOI: | 10.1038/s42003-024-05781-x |
Abstrakt: | Cannabinol (CBN), an incompletely understood metabolite for ∆9-tetrahydrocannabinol, has been suggested as an analgesic. CBN interacts with endocannabinoid (CB) receptors, but is also reported to interact with non-CB targets, including various ion channels. We assessed CBN effects on voltage-dependent sodium (Nav) channels expressed heterologously and in native dorsal root ganglion (DRG) neurons. Our results indicate that CBN is a functionally-selective, but structurally-non-selective Nav current inhibitor. CBN's main effect is on slow inactivation. CBN slows recovery from slow-inactivated states, and hyperpolarizes steady-state inactivation, as channels enter deeper and slower inactivated states. Multielectrode array recordings indicate that CBN attenuates DRG neuron excitability. Voltage- and current-clamp analysis of freshly isolated DRG neurons via our automated patch-clamp platform confirmed these findings. The inhibitory effects of CBN on Nav currents and on DRG neuron excitability add a new dimension to its actions and suggest that this cannabinoid may be useful for neuropathic pain. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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