Flunarizine blocks voltage-gated Na⁺ and Ca²⁺ currents in cultured rat cortical neurons: A possible locus of action in the prevention of migraine

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• 作者：Qing Ye^a ; Lan-Yun Yan^a ; Liu-Jun Xue^a ; Qiang Wang^b ; Zhi-Kui Zhou^a ; Hiang Xiao^b ; Qi Wan^a ; ^{chinaqiwan@126.com}
• 关键词：Flunarizine ; Migraine ; Sodium current ; Calcium current ; Patch-clamp recording ; Cortical neurons
• 刊名：Neuroscience Letters
• 出版年：2011
• 出版时间：10 January 2011
• 年：2011
• 卷：487
• 期：3
• 页码：394-399
• 全文大小：674 K

文摘

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⁺ and Ca²⁺ 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⁺ and Ca²⁺ channels of cultured rat cortical neurons. Sodium currents (I_Na) and calcium currents (I_Ca) in cultured rat cortical neurons were monitored using whole-cell patch-clamp recordings. Both I_Na and I_Ca were blocked by FLN in a concentration-dependent manner with IC₅₀ values of 0.94 μM and 1.77 μM, respectively. The blockade of I_Na was more powerful at more depolarizing holding potentials. The steady-state inactivation curve of I_Na was shifted towards more hyperpolarizing potentials by FLN. FLN significantly delayed the recovery from fast inactivation of I_Na. Furthermore, the action of FLN in blocking I_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.