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首页> 外文期刊>Neuron >Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current.
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Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current.

机译：钠通道β4的细胞质尾巴通过开放通道阻滞，作为钠电流恢复的机制。

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摘要

Voltage-gated sodium channels with "resurgent" kinetics are specialized for high-frequency firing. The alpha subunits interact with a blocking protein that binds open channels upon depolarization and unbinds upon repolarization, producing resurgent sodium current. By limiting classical inactivation, the cycle of block and unblock shortens refractory periods. To characterize the blocker in Purkinje neurons, we briefly exposed inside-out patches to substrate-specific proteases. Trypsin and chymotrypsin each removed resurgent current, consistent with established roles for positively charged and hydrophobic/aromatic groups in blocking sodium channels. In Purkinje cells, the only known sodium channel-associated subunit that has a cytoplasmic sequence with several positive charges and clustered hydrophobic/aromatic residues is beta4 (KKLITFILKKTREK; beta4(154-167)). After enzymatic removal of block, beta4(154-167) fully reconstituted resurgent current, whereas scrambled or point-mutated peptides were ineffective. In CA3 pyramidal neurons, which lack beta4 and endogenous block, beta4(154-167) generated resurgent current. Thus, beta4 may be the endogenous open-channel blocker responsible for resurgent kinetics.
机译：具有“恢复”动力学的电压门控钠通道专门用于高频点火。 α亚基与阻断蛋白相互作用，该阻断蛋白在去极化时结合开放通道，在再极化时解除结合，从而产生复苏的钠电流。通过限制经典的灭活，封闭和解除封闭的周期缩短了不应期。为了表征浦肯野神经元中的阻滞剂，我们简要地将内而外的补丁暴露于底物特异性蛋白酶。胰蛋白酶和胰凝乳蛋白酶各自去除了回潮电流，这与在封闭钠通道中带正电和疏水/芳香基团的既定作用保持一致。在Purkinje细胞中，唯一已知的具有多个正电荷且聚集了疏水/芳族残基的胞质序列的钠通道相关亚基是beta4（KKLITFILKKTREK; beta4（154-167））。在酶促去除阻断后，beta4（154-167）完全恢复了复苏电流，而混乱或点突变的肽无效。在缺乏beta4和内源性阻断的CA3锥体神经元中，beta4（154-167）产生了复苏电流。因此，beta4可能是内源性的开放通道阻滞剂，负责复苏动力学。

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