Use-dependent potentiation of the Nav1.6 sodium channel.
Use-dependent potentiation of the Nav1.6 sodium channel.
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DOI：
10.1529/biophysj.104.045963
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发表时间：
2004-12
影响因子：
3.4
通讯作者：
W. Zhou;A. Goldin
中科院分区：
文献类型：
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作者：
W. Zhou;A. Goldin
Nav1.2 和 Nav1.6 是成人中枢神经系统中丰富的两种电压门控钠通道亚型。这些通道在不同的细胞中表达并位于不同的神经元区域，这可能反映了功能的专业化。为了检验这种可能性，我们比较了 Nav1.2 和 Nav1.6 响应一系列快速重复去极化的特性。通过与 beta1 共表达的 Nav1.6 的电流在快速去极化过程中表现出依赖于使用的增强作用。这种增强作用与 Nav1.2 与 beta1 的电流依赖性下降形成鲜明对比。增强的电压依赖性与激活的电压依赖性相关，并且当通过突变去除快速失活时，它仍然发生。快速刺激加速了 Nav1.6 通道中的缓慢激活阶段，该通道已消除快速失活，从而导致更快的通道激活。尽管去除快速失活的 Nav1.2 通道也表现出稍快的激活，但与 Nav1.6 相比，该通道表现出非常明显的缓慢失活。这些结果表明 Nav1.6 钠电流的增强是由更快的通道激活引起的，而这种效应被 Nav1.2 中的缓慢失活所掩盖。数据表明，Nav1.6 可能更能抵抗失活，与 Nav1.2 相比，这可能有助于朗飞节点的高频发射。
Nav1.2 and Nav1.6 are two voltage-gated sodium channel isoforms that are abundant in the adult central nervous system. These channels are expressed in different cells and localized in different neuronal regions, which may reflect functional specialization. To examine this possibility, we compared the properties of Nav1.2 and Nav1.6 in response to a rapid series of repetitive depolarizations. Currents through Nav1.6 coexpressed with beta1 demonstrated use-dependent potentiation during a rapid train of depolarizations. This potentiation was in contrast to the use-dependent decrease in current for Nav1.2 with beta1. The voltage dependence of potentiation correlated with the voltage dependence of activation, and it still occurred when fast inactivation was removed by mutation. Rapid stimulation accelerated a slow phase of activation in the Nav1.6 channel that had fast inactivation removed, resulting in faster channel activation. Although the Nav1.2 channel with fast inactivation removed also demonstrated slightly faster activation, that channel showed very pronounced slow inactivation compared to Nav1.6. These results indicate that potentiation of Nav1.6 sodium currents results from faster channel activation, and that this effect is masked by slow inactivation in Nav1.2. The data suggest that Nav1.6 might be more resistant to inactivation, which might be helpful for high-frequency firing at nodes of Ranvier compared to Nav1.2.