Zona C, Ciotti M T, Avoli M
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Roma Tor Vergata, Rome, Italy.
Neurosci Lett. 1997 Aug 15;231(3):123-6. doi: 10.1016/s0304-3940(97)00543-0.
Whole-cell, voltage-clamp recordings were made from rat cerebellar granule cells in culture under experimental conditions designed to study voltage-gated Na+ currents that were elicited by depolarizing commands from a holding potential of -60 mV up to +20 mV. These tetrodotoxin-sensitive inward currents were reduced in a dose-related manner by bath application of the structurally novel, anticonvulsant drug topiramate (10-1000 microM; n = 16). Dose-response analysis of this effect revealed an IC50 of 48.9 microM. Topiramate also made the steady-state inactivation curve of this current shift toward more negative values (midpoint of the inactivation curve -46.9 mV under control conditions and -56.5 mV during topiramate application; n = 5). We propose that these effects may contribute to control the sustained depolarizations with repetitive firing of action potentials that occur within neuronal networks during seizure activity. Therefore they may represent a mechanism of action for this novel anticonvulsant drug.
在旨在研究电压门控钠电流的实验条件下，对培养的大鼠小脑颗粒细胞进行全细胞电压钳记录。电压门控钠电流由从-60 mV的钳制电位到+20 mV的去极化指令诱发。通过浴加结构新颖的抗惊厥药物托吡酯（10 - 1000 μM；n = 16），这些对河豚毒素敏感的内向电流以剂量相关的方式减少。对该效应的剂量反应分析显示IC50为48.9 μM。托吡酯还使该电流的稳态失活曲线向更负的值移动（对照条件下失活曲线的中点为-46.9 mV，托吡酯应用期间为-56.5 mV；n = 5）。我们认为，这些效应可能有助于控制癫痫发作活动期间神经元网络内发生的动作电位重复发放所导致的持续去极化。因此，它们可能代表了这种新型抗惊厥药物的一种作用机制。
