Research Division for Life Sciences, Kumamoto Health Science University, Japan.
J Pharmacol Sci. 2012;118(1):33-42. doi: 10.1254/jphs.11060fp. Epub 2011 Dec 10.
Recent studies have demonstrated that the botulinum neurotoxins inhibit the release of acetylcholine, glutamate, GABA, and glycine in central nerve system (CNS) neurons. The Na(+) current (I(Na)) is of major interest because it acts as the trigger for many cellular functions such as transmission, secretion, contraction, and sensation. Thus, these observations raise the possibility that A type neurotoxin might also alter the I(Na) of neuronal excitable membrane. To test our idea, we examined the effects of A type neurotoxins on I(Na) of central and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations produced substantial decreases of the neuronal I(Na), but interestingly the current inhibition was saturated at about maximum 50% level of control I(Na). The inhibitory pattern in the concentration-response curve for the neurotoxins differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that completely inhibited I(Na) in a concentration-dependent manner. We concluded that A type neurotoxins inhibited membrane Na(+)-channel activity in CNS neurons and that I(Na) of both TTX-sensitive and -insensitive peripheral dorsal ganglion cells were also inhibited similarly to a maximum 40% of the control by the neurotoxins. The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain.
最近的研究表明，肉毒杆菌神经毒素抑制中枢神经系统（CNS）神经元中乙酰胆碱、谷氨酸、GABA 和甘氨酸的释放。钠离子电流（I(Na)）是主要关注点，因为它作为许多细胞功能的触发因素，如传递、分泌、收缩和感觉。因此，这些观察结果提出了 A 型神经毒素也可能改变神经元可兴奋膜的 I(Na)的可能性。为了验证我们的想法，我们检查了 A 型神经毒素对中枢和周围神经元 I(Na)的影响。纳摩尔至皮摩尔浓度的神经毒素产生了神经元 I(Na)的显著减少，但有趣的是，电流抑制在约 50%的对照 I(Na)的最大水平处饱和。神经毒素在浓度反应曲线上的抑制模式与河豚毒素（TTX）、局部麻醉剂和抗癫痫药物不同，它们以浓度依赖性方式完全抑制 I(Na)。我们得出结论，A 型神经毒素抑制中枢神经系统神经元的膜 Na(+)-通道活性，并且 I(Na)的 TTX 敏感和不敏感的外周背根神经节细胞也被神经毒素抑制至约 40%的对照水平。结果表明，A2NTX 也可作为治疗癫痫和多种类型疼痛的有效药物。
