Castillo Juan P, Rui Huan, Basilio Daniel, Das Avisek, Roux Benoît, Latorre Ramon, Bezanilla Francisco, Holmgren Miguel
1] Laboratorio de Fisiología Celular, Facultad de Ciencias, Universidad de Chile, Montemar 254006, Chile [2] Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2366103, Chile.
Department of Biochemistry and Molecular Biology, University of Chicago, Gordon Center for Integrative Sciences, Chicago, Illinois 60637, USA.
Nat Commun. 2015 Jul 24;6:7622. doi: 10.1038/ncomms8622.
The Na(+)/K(+)-ATPase restores sodium (Na(+)) and potassium (K(+)) electrochemical gradients dissipated by action potentials and ion-coupled transport processes. As ions are transported, they become transiently trapped between intracellular and extracellular gates. Once the external gate opens, three Na(+) ions are released, followed by the binding and occlusion of two K(+) ions. While the mechanisms of Na(+) release have been well characterized by the study of transient Na(+) currents, smaller and faster transient currents mediated by external K(+) have been more difficult to study. Here we show that external K(+) ions travelling to their binding sites sense only a small fraction of the electric field as they rapidly and simultaneously become occluded. Consistent with these results, molecular dynamics simulations of a pump model show a wide water-filled access channel connecting the binding site to the external solution. These results suggest a mechanism of K(+) gating different from that of Na(+) occlusion.
钠钾ATP酶可恢复因动作电位和离子偶联转运过程而消散的钠(Na⁺)和钾(K⁺)电化学梯度。离子在运输过程中会短暂被困在细胞内和细胞外门之间。一旦外部门打开,三个Na⁺离子被释放,随后两个K⁺离子结合并被封闭。虽然通过对瞬时Na⁺电流的研究已很好地阐明了Na⁺释放机制,但由外部K⁺介导的更小、更快的瞬时电流则更难研究。在此我们表明,向其结合位点移动的外部K⁺离子在迅速且同时被封闭时,仅感知到一小部分电场。与这些结果一致,泵模型的分子动力学模拟显示出一条宽阔的充满水的通道,将结合位点与外部溶液相连。这些结果提示了一种与Na⁺封闭不同的K⁺门控机制。