阿米替林对伤害性三叉神经神经元中河豚毒素不敏感的 Nav1.9 电流的影响。
Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons.
机构信息
Department of Neurology, Chinese PLA General Hospital, Beijing 100853, PR China.
出版信息
Mol Pain. 2013 Jun 22;9:31. doi: 10.1186/1744-8069-9-31.
BACKGROUND
Amitriptyline (AMI) is tricyclic antidepressant that has been widely used to manage various chronic pains such as migraines. Its efficacy is attributed to its blockade of voltage-gated sodium channels (VGSCs). However, the effects of AMI on the tetrodotoxin-resistant (TTX-r) sodium channel Nav1.9 currents have been unclear to present.
RESULTS
Using a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Nav1.9 currents in a concentration-dependent manner and had an IC50 of 15.16 μM in acute isolated trigeminal ganglion (TG) neurons of the rats. 10 μM AMI significantly shifted the steady-state inactivation of Nav1.9 channels in the hyperpolarizing direction without affecting voltage-dependent activation. Surprisingly, neither 10 nor 50 μM AMI caused a use-dependent blockade of Nav1.9 currents elicited by 60 pulses at 1 Hz.
CONCLUSION
These data suggest that AMI is a state-selective blocker of Nav1.9 channels in rat nociceptive trigeminal neurons, which likely contributes to the efficacy of AMI in treating various pains, including migraines.
背景
阿米替林（AMI）是一种三环类抗抑郁药，已广泛用于治疗偏头痛等各种慢性疼痛。其疗效归因于其对电压门控钠离子通道（VGSCs）的阻断作用。然而，阿米替林对河豚毒素抗性（TTX-r）钠离子通道 Nav1.9 电流的影响目前尚不清楚。
结果
本研究采用全细胞膜片钳技术，显示阿米替林以浓度依赖性方式有效抑制 Nav1.9 电流，在急性分离的大鼠三叉神经节（TG）神经元中，IC50 为 15.16 μM。10 μM AMI 可显著将 Nav1.9 通道的稳态失活向超极化方向移动，而不影响电压依赖性激活。令人惊讶的是，10 μM 和 50 μM AMI 均不会导致 Nav1.9 电流产生使用依赖性阻断，Nav1.9 电流由 1 Hz 时的 60 个脉冲诱发。
结论
这些数据表明，阿米替林是大鼠伤害性三叉神经神经元中 Nav1.9 通道的状态选择性阻断剂，这可能有助于 AMI 治疗各种疼痛（包括偏头痛）的疗效。
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