Tamadon Hanieh, Ghasemi Zahra, Ghasemi Fatemeh, Hosseinmardi Narges, Vatanpour Hossein, Janahmadi Mahyar
Department of Physiology, Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Tarbiat Modares University, Tehran, Iran.
Basic Clin Neurosci. 2019 Jan-Feb;10(1):49-58. doi: 10.32598/bcn.9.10.350. Epub 2019 Jan 1.
It is a long time that natural toxin research is conducted to unlock the medical potential of toxins. Although venoms-toxins cause pathophysiological conditions, they may be effective to treat several diseases. Since toxins including scorpion toxins target voltage-gated ion channels, they may have profound effects on excitable cells. Therefore, elucidating the cellular and electrophysiological impacts of toxins, particularly scorpion toxins would be helpful in future drug development opportunities.
Intracellular recording was made from F1 cells of Helix aspersa in the presence of calcium Ringer solution in which Na and K channels were blocked. Then, the modulation of channel function in the presence of extracellular application of F4 and F6 toxins and kaliotoxin (KTX; 50 nM and 1 μM) was examined by assessing the electrophysiological characteristics of calcium spikes.
The two active toxin fractions, similar to KTX, a known Ca-activated K channel blocker, reduced the amplitude of AHP, enhanced the firing frequency of calcium spikes and broadened the duration of Ca spikes. Therefore, it might be inferred that these two new fractions induce neuronal hyperexcitability possibly, in part, by blocking calcium-activated potassium channel current. However, this supposition requires further investigation using voltage clamping technique.
These toxin fractions may act as blocker of calcium-activated potassium channels.
对天然毒素进行研究以挖掘毒素的医学潜力已有很长时间。尽管毒液毒素会引发病理生理状况，但它们可能对治疗多种疾病有效。由于包括蝎毒素在内的毒素靶向电压门控离子通道，它们可能对可兴奋细胞产生深远影响。因此，阐明毒素尤其是蝎毒素的细胞和电生理影响，将有助于未来的药物开发。
在存在钙林格溶液（其中钠和钾通道被阻断）的情况下，从欧洲花园蜗牛的F1细胞进行细胞内记录。然后，通过评估钙尖峰的电生理特征，研究在细胞外应用F4和F6毒素以及 kaliotoxin（KTX；50 nM和1 μM）时通道功能的调节情况。
这两个活性毒素组分，与已知的钙激活钾通道阻滞剂KTX类似，降低了后超极化（AHP）的幅度，提高了钙尖峰的发放频率并拓宽了钙尖峰的持续时间。因此，可以推断这两个新组分可能部分通过阻断钙激活钾通道电流来诱导神经元兴奋性过高。然而，这一推测需要使用电压钳技术进行进一步研究。
这些毒素组分可能作为钙激活钾通道的阻滞剂。
