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首页> 外文期刊>The European Journal of Neuroscience >Persistent sodium current in subicular neurons isolated from patients with temporal lobe epilepsy.
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Persistent sodium current in subicular neurons isolated from patients with temporal lobe epilepsy.

机译:从颞叶癫痫患者中分离出的亚皮层神经元持续存在钠电流。

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Abstract The persistent sodium current is a common target of anti-epileptic drugs and contributes to burst firing. Intrinsically burst firing subicular neurons are involved in the generation and spread of epileptic activity. We measured whole-cell sodium currents in pyramidal neurons isolated from the subiculum resected in drug-resistant epileptic patients and in rats. In half of the cells from both patients and rats, the sodium current inactivated within 500 ms at -30 mV. Others displayed a tetrodotoxin-sensitive slowly or non-inactivating sodium current of up to 53% of the total sodium current amplitude. Compared with the transient sodium current in the same cells, this persistent sodium current activated with normal kinetics but its voltage-dependent activation occurred 7 mV more hyperpolarized. Depolarizing voltage steps that lasted 10 s completely inactivated the persistent sodium current. Its voltage dependence did not differ from that of the transient sodium current but its slope was less steep.The voltage dependence and kinetics of the persistent sodium current in cells from patients were not different from that in subicular cells from rats. The current density and the relative amplitude contribution were 3-4 times greater in neurons from drug-resistant epilepsy patients. The abundant presence of persistent sodium current in half of the subicular neurons could lead to a larger number of neurons with intrinsic burst firing. The extraordinarily large amplitude of the persistent sodium current in this subset of subicular neurons might explain why these patients are susceptible to seizures and hard to treat pharmacologically.
机译:摘要持续存在的钠电流是抗癫痫药物的常见靶标,并有助于爆发性放电。内源性放电激发的皮下神经元参与癫痫活动的产生和传播。我们测量了从耐药性癫痫患者和大鼠切除的亚细核分离的锥体神经元中的全细胞钠电流。在来自患者和大鼠的一半细胞中,钠电流在-30 mV的500毫秒内失活。其他人则表现出对河豚毒素敏感的缓慢或非灭活钠电流,最高可达总钠电流幅度的53%。与相同细胞中的瞬时钠电流相比,这种持续的钠电流以正常动力学激活,但其电压依赖性激活发生了7 mV的超极化。持续10 s的去极化电压阶跃完全使持续的钠电流失活。它的电压依赖性与瞬时钠电流没有什么不同,但其斜率不那么陡峭。患者细胞中的持续钠电流的电压依赖性和动力学与大鼠亚特异性细胞中的电压依赖性和动力学没有差异。耐药性癫痫患者神经元的电流密度和相对幅度贡献要大3-4倍。一半的亚皮层神经元中大量存在持续性钠电流,可能导致大量具有内在爆发力的神经元。在这部分亚皮层神经元中持续钠电流的异常大幅度可能解释了为什么这些患者易患癫痫发作并且难以进行药理治疗。

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