Osthol is a use-dependent blocker of voltage-gated Na+ channels in mouse neuroblastoma N2A cells.
Osthol, a Chinese herbal compound, has been shown to possess vasorelaxant and neuroprotective properties. Not much is known about the effects of osthol on ionic channels, activities of which are implicated in vasorelaxation and neuroprotection. In this work we report that osthol could inhibit voltage-gated Na (+) currents with state-dependence in mouse neuroblastoma N2A cells (IC (50) = 12.3 microM and 31.5 microM at holding potentials of - 70 mV and - 100 mV, respectively). Current blockade was equally effective in both extracellular and intracellular application of osthol. Osthol (18 microM) did not significantly affect the kinetics and voltage-dependence of Na (+) channel activation, but left-shifted the steady-state inactivation curve (V (1/2) = - 60.5 mV and - 78.7 mV in the absence and presence of osthol, respectively). Osthol also mildly but significantly retarded channel recovery from inactivation (recovery time constant = 19.9 ms and 35.6 ms in the absence and presence of osthol, respectively). In addition, osthol blocked Na (+) currents in a frequency-dependent fashion: blockades of 17 %, 34 % and 49 % when currents were triggered at 0.33 Hz, 1 Hz and 3.33 Hz, respectively. Taken together, our results therefore suggest that osthol blocked voltage-gated Na (+) channels intracellularly with state- and frequency-dependence.
Leung
Yuk-Man
YM
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. ymleung@mail.cmu.edu.tw
Kuo
Yueh-Hsiung
YH
Chao
Chia-Chia
CC
Tsou
Yi-Huan
YH
Chou
Chun-Hsiao
CH
Lin
Chia-Huei
CH
Wong
Kar-Lok
KL
D000818:Animals; D045744:Cell Line, Tumor; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D019684:Magnoliopsida / Q000737:chemistry*; D051379:Mice; D009369:Neoplasms; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008517:Phytotherapy; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*
D003374:Coumarins; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C046627:osthol