Department of Pediatrics, Chi-Mei Medical Center, Tainan 710, Taiwan.
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Int J Mol Sci. 2020 Nov 4;21(21):8254. doi: 10.3390/ijms21218254.
OD-1, a scorpion toxin, has been previously recognized as an activator of voltage-gated Na currents. To what extent this agent can alter hippocampal neuronal Na currents and network excitability and how it can be applied to neuronal hyperexcitability research remains unclear. With the aid of patch-clamp technology, it was revealed that, in mHippoE-14 hippocampal neurons, OD-1 produced a concentration-, time-, and state-dependent rise in the peak amplitude of . It shifted the inactivation curve to a less negative potential and increased the frequency of spontaneous action currents. Further characterization of neuronal excitability revealed higher excitability in the hippocampal slices treated with OD-1 as compared with the control slices. A stereotaxic intrahippocampal injection of OD-1 generated a significantly higher frequency of spontaneous seizures and epileptiform discharges compared with intraperitoneal injection of lithium-pilocarpine- or kainic acid-induced epilepsy, with comparable pathological changes. Carbamazepine significantly attenuated OD-1 induced seizures and epileptiform discharges. The OD-1-mediated modifications of altered the electrical activity of neurons in vivo and OD-1 could potentially serve as a novel seizure and excitotoxicity model.
OD-1 是一种蝎子毒素，先前被认为是一种电压门控 Na+电流的激活剂。该试剂在何种程度上可以改变海马神经元 Na+电流和网络兴奋性，以及如何将其应用于神经元过度兴奋的研究，目前尚不清楚。借助膜片钳技术，研究人员发现，在 mHippoE-14 海马神经元中，OD-1 会浓度、时间和状态依赖性地增加峰值幅度。它使失活曲线向更负的电位偏移，并增加自发动作电流的频率。进一步对神经元兴奋性进行表征发现，与对照组切片相比，用 OD-1 处理的海马切片具有更高的兴奋性。与腹腔内注射锂-匹罗卡品或海人酸诱导的癫痫相比，立体定向海马内注射 OD-1 会产生更高频率的自发性癫痫发作和癫痫样放电，且具有相似的病理变化。卡马西平可显著减轻 OD-1 诱导的癫痫发作和癫痫样放电。OD-1 介导的改变改变了神经元的电活动，OD-1 可能成为一种新型的癫痫和兴奋毒性模型。
