Flunarizine blocks voltage-gated Na super(+) and Ca super(2+) currents in cultured rat cortical neurons: A possible locus of action in the prevention of migraine

• Published in: Neuroscience letters 2011-01, Vol.487 (3), p.394-399
• Main Authors: Ye, Qing, Yan, Lan-Yun, Xue, Liu-Jun, Wang, Qiang, Zhou, Zhi-Kui, Xiao, Hiang, Wan, Qi
• Format: Article
• Language: English
• ISSN: 0304-3940
• DOI: 10.1016/j.neulet.2010.10.064

Although flunarizine (FLN) has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. It has been hypothesized that migraine is a channelopathy, and abnormal activities of voltage-gated Na super(+) and Ca super(2+) channels might represent a potential mechanism of cortical hyperexcitability predisposing to migraine. The aim of the present study was to investigate the effects of FLN on Na super(+) and Ca super(2+) channels of cultured rat cortical neurons. Sodium currents (I sub(Na)) and calcium currents (I sub(Ca)) in cultured rat cortical neurons were monitored using whole-cell patch-clamp recordings. Both I sub(Na) and I sub(Ca) were blocked by FLN in a concentration-dependent manner with IC sub(50) values of 0.94 mu M and 1.77 mu M, respectively. The blockade of I sub(Na) was more powerful at more depolarizing holding potentials. The steady-state inactivation curve of I sub(Na) was shifted towards more hyperpolarizing potentials by FLN. FLN significantly delayed the recovery from fast inactivation of I sub(Na). Furthermore, the action of FLN in blocking I sub(Na) was enhanced at higher rates of channel activation. Blockades of these currents might help explain the mechanism underlying the preventive effect of FLN on migraine attacks.