Inhibition of voltage-gated Na+ channels by hinokiol in neuronal cells

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: ic50 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. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.