title: Flunarizine inhibits sensory neuron excitability by blocking voltage-gated Na+ and Ca2+ currents in trigeminal ganglion neurons.
abstract: 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 Ca(2+) 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.
  
  
  CONCLUSIONS
  Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks.
authors: Department of Neurology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Qing
authors: Q
authors: Ye
authors: Qiang
authors: Q
authors: Wang
authors: Lan-yun
authors: LY
authors: Yan
authors: Wen-hui
authors: WH
authors: Wu
authors: Sha
authors: S
authors: Liu
authors: Hang
authors: H
authors: Xiao
authors: Qi
authors: Q
authors: Wan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005444:Flunarizine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D012964:Sodium; D005444:Flunarizine; D002118:Calcium