Biophysical characterisation of the persistent sodium current of the Nav1.6 neuronal sodium channel: a single-channel analysis
Biophysical characterisation of the persistent sodium current of the Nav1.6 neuronal sodium channel: a single-channel analysis
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DOI：
10.1007/s00424-010-0801-9
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发表时间：
2010-06-01
影响因子：
4.5
通讯作者：
Chahine, Mohamed
中科院分区：
文献类型：
--
作者：
Chatelier, Aurelien;Zhao, Juan;Chahine, Mohamed
Na(v)1.6 是 Ranvier 节点处主要的电压门控钠通道。在全细胞实验中，该通道已被证明可以产生强大的持续内向电流。 Na(v)1.6 在轴突传导中发挥重要作用，并可能通过这种持续电流对受损神经系统的病理生理学产生显着影响。然而，持续电流的潜在分子机制和调节尚不清楚。使用膜片钳技术的全细胞配置，我们研究了 HEK-293 中的 Na(v)1.6 瞬态和持续电流。先前的研究表明，持续电流取决于贴片电极的含量。因此，我们使用膜片钳技术的细胞附着配置来表征具有完整细胞内介质的持续电流的单通道特性。在 HEK-293 细胞中，全细胞配置中记录的 Na(v)1.6 持续电流为峰值瞬态电流的 3-5%。在单通道记录中，峰值与持续开路概率之间的比率证实了在全细胞配置中观察到的持续电流的大小。细胞附着结构揭示了全细胞持续电流的分子机制是单个Na(v)1.6通道重新开放的结果。
Na(v)1.6 is the major voltage-gated sodium channel at nodes of Ranvier. This channel has been shown to produce a robust persistent inward current in whole-cell experiments. Na(v)1.6 plays an important role in axonal conduction and may significantly contribute to the pathophysiology of the injured nervous system through this persistent current. However, the underlying molecular mechanisms and regulation of the persistent current are not well understood. Using the whole-cell configuration of the patch-clamp technique, we investigated the Na(v)1.6 transient and persistent currents in HEK-293. Previous studies have shown that the persistent current depended on the content of the patch electrode. Therefore, we characterised the single-channel properties of the persistent current with an intact intracellular medium using the cell-attached configuration of the patch-clamp technique. In HEK-293 cells, the Na(v)1.6 persistent current recorded in the whole-cell configuration was 3-5% of the peak transient current. In single-channel recording, the ratio between peak and persistent open probability confirmed the magnitude of the persistent current observed in the whole-cell configuration. The cell-attached configuration revealed that the molecular mechanism of the whole-cell persistent current is a consequence of single Na(v)1.6 channels reopening.