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Flunarizine inhibits sensory neuron excitability by blocking voltage-gated Na+ and Ca2+ currents in trigeminal ganglion neurons

摘要Background Although flunarizine has been widely used for migraine prophylaxis with clear success,the mechanisms of its actions in migraine prophylaxis are not completely understood.The aim of this study was to investigate the effects of flunarizine on tetrodotoxin-resistant Na+ channels and high-voltage activated Ca2+ channels of acutely isolated mouse trigeminal ganglion neurons.Methods Sodium currents and calcium currents in trigeminal ganglion neurons were monitored using whole-cell patch-clamp recordings.Paired Student's t test was used as appropriate to evaluate the statistical significance of differences between two group means.Results Both tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were blocked by flunarizine in a concentration-dependent manner with the concentration producing half-maximal current block values of 2.89 μmol/L and 2.73 μmol/L,respectively.The steady-state inactivation curves of tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were shifted towards more hyperpolarizing potentials after exposure to flunarizine.Furthermore,the actions of flunarizine in blocking tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were use-dependent,with effects enhanced at higher rates of channel activation.Conclusion Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks.

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DOI 10.3760/cma.j.issn.0366-6999.2011.17.015
发布时间 2011-11-11(万方平台首次上网日期,不代表论文的发表时间)
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中华医学杂志(英文版)

中华医学杂志(英文版)

2011年124卷17期

2649-2655页

SCIMEDLINEISTICCSCDCABP

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