Shin Min-Chul, Wakita Masahito, Xie Du-Jie, Yamaga Toshitaka, Iwata Satomi, Torii Yasushi, Harakawa Tetsuhiro, Ginnaga Akihiro, Kozaki Shunji, Akaike Norio
Research Division for Life Sciences, Kumamoto Health Science University, Kumamoto 861-5598, Japan.
Research Division for Life Sciences, Kumamoto Health Science University, Kumamoto 861-5598, Japan; Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
J Pharmacol Sci. 2012;118(1):33-42. doi: 10.1254/jphs.11060FP. Epub 2019 Jun 11.
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) 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 of neuronal excitable membrane. To test our idea, we examined the effects of A type neurotoxins on I of central and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations produced substantial decreases of the neuronal I, but interestingly the current inhibition was saturated at about maximum 50% level of control I. The inhibitory pattern in the concentration-response curve for the neurotoxins differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that completely inhibited I in a concentration-dependent manner. We concluded that A type neurotoxins inhibited membrane Na-channel activity in CNS neurons and that I 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，肉毒杆菌神经毒素会抑制中枢神经系统（CNS）神经元中乙酰胆碱、谷氨酸、γ-氨基丁酸和甘氨酸的释放。钠电流（I）备受关注，因为它是许多细胞功能（如传递、分泌、收缩和感觉）的触发因素。因此，这些观察结果增加了A型神经毒素也可能改变神经元兴奋性膜电流的可能性。为了验证我们的想法，我们研究了A型神经毒素对中枢和外周神经元电流的影响。飞摩尔到皮摩尔浓度的神经毒素使神经元电流大幅下降，但有趣的是，电流抑制在约为对照电流最大值50%的水平时达到饱和。神经毒素浓度-反应曲线中的抑制模式不同于河豚毒素（TTX）、局部麻醉药和抗癫痫药物，它们以浓度依赖的方式完全抑制电流。我们得出结论，A型神经毒素抑制中枢神经系统神经元中的膜钠通道活性，并且TTX敏感和不敏感的外周背根神经节细胞的电流也被神经毒素类似地抑制，最大抑制程度为对照的40%。结果显然表明，A2NTX也可作为治疗癫痫和几种疼痛的有效药物。
