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Inhibition of voltage-gated Na+ channels by hinokiol in neuronal cells
- Source :
- Pharmacological Reports. 67:1049-1054
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Background Hinokiol is a naturally occurring diterpenoid compound isolated from plants such as Taiwania cryptomerioides . Anti-oxidation, anti-cancer, and anti-inflammation effects of this compound have been reported. It is not yet known if hinokiol affects neurons or neuronal ion channel activities. We reported here that hinokiol inhibited voltage-gated Na + channels (VGSC) in neuronal cells and we characterized the mechanisms of block. Methods The effects of hinokiol on Na + channels were examined using the voltage-clamp (whole-cell mode) technique. Results VGSC was blocked by hinokiol in a concentration-dependent and state-dependent manner in neuroblastoma N2A cells: IC 50 are 11.3 and 37.4 μM in holding potentials of −70 and −100 mV, respectively. In the presence of hinokiol there was a 13-mV left shift in steady-state inactivation curves; however, activation gating was not altered. VGSC inhibition by hinokiol did not require channel opening and was thus considered to be closed-channel block. In the presence of hinokiol, since the degree of block did not enhance with stimulation frequency, block by hinokiol thus did not exhibit use-dependence. Recovery from channel inactivation was not significantly affected in the presence of hinokiol. In addition, hinokiol also inhibited VGSC of differentiated neuronal NG108-15 cells and rat hippocampal CA1 neurons. Conclusion Our results therefore suggest hinokiol inhibited VGSC in a closed-channel block manner and such inhibition involved intensification of channel inactivation.
- Subjects :
- Neurons
Voltage-Gated Sodium Channel Blockers
Pharmacology
Dose-Response Relationship, Drug
Voltage-gated ion channel
Chemistry
Stimulation
Voltage-Gated Sodium Channels
General Medicine
Gating
Hippocampal formation
medicine.disease
Cell Line
Membrane Potentials
Rats
Neuroblastoma
Abietanes
medicine
Biophysics
Animals
CA1 Region, Hippocampal
Neuroscience
Taiwania cryptomerioides
Ion channel
Subjects
Details
- ISSN :
- 17341140
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Pharmacological Reports
- Accession number :
- edsair.doi.dedup.....4fd5ed368cb73cce5fbc250f066ad8d0