The Na+/K+-ATPase is a chemical molecular machine responsible for the movement of Na+ and K+ ions across the cell membrane. These ions are moved against their electrochemical gradients, so the protein uses the free energy of ATP hydrolysis to transport them. In fact, the Na+/K+-ATPase is the single largest consumer of energy in most cells. In each pump cycle, the protein sequentially exports 3Na+ out of the cell, then imports 2K+ into the cell at an approximate rate of 200 cycles/s. In each half cycle of the transport process, there is a state in which ions are stably trapped within the permeation pathway of the protein by internal and external gates in their closed states. These gates are required to open alternately; otherwise, passive ion diffusion would be a wasteful end of the cell’s energy. Once one of these gates open, ions diffuse from their binding sites to the accessible milieu, which involves moving through part of the electrical field across the membrane. Consequently, ions generate transient electrical currents first discovered more than 30 years ago. They have been studied in a variety of preparations, including native and heterologous expression systems. Here, we review three decades’ worth of work using these transient electrical signals to understand the kinetic transitions of the movement of Na+ and K+ ions through the Na+/K+-ATPase and propose the significance that this work might have to the understanding of the dysfunction of human pump orthologs responsible for some newly discovered neurological pathologies.

中文翻译：

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Na+/K+-ATPase 介导的瞬态电流：从基本生物物理学到人类疾病的旅程。

Na+/K+-ATPase 是一种化学分子机器，负责 Na+ 和 K+ 离子穿过细胞膜的运动。这些离子逆着它们的电化学梯度移动，因此蛋白质利用 ATP 水解的自由能来运输它们。事实上，Na+/K+-ATPase 是大多数细胞中最大的单一能量消耗者。在每个泵循环中，蛋白质依次将 3Na+ 输出到细胞外，然后以大约 200 个循环/秒的速率将 2K+ 输入到细胞中。在运输过程的每个半周期中，都有一种状态，即离子在关闭状态下被内门和外门稳定地捕获在蛋白质的渗透途径中。这些闸门需要交替开启；否则，被动离子扩散将浪费电池能量。一旦其中一扇门打开，离子从它们的结合位点扩散到可接近的环境，这涉及穿过部分电场穿过膜。因此，离子产生瞬态电流是在 30 多年前首次发现的。它们已在各种制剂中进行了研究，包括天然和异源表达系统。在这里，我们回顾了过去三年的工作，使用这些瞬态电信号来了解 Na+ 和 K+ 离子通过 Na+/K+-ATPase 运动的动力学转变，并提出这项工作可能对理解功能障碍的重要性负责一些新发现的神经病理学的人类泵直向同源物。离子产生瞬态电流是在 30 多年前首次发现的。它们已在各种制剂中进行了研究，包括天然和异源表达系统。在这里，我们回顾了过去三年的工作，使用这些瞬态电信号来了解 Na+ 和 K+ 离子通过 Na+/K+-ATPase 运动的动力学转变，并提出这项工作可能对理解功能障碍的重要性负责一些新发现的神经病理学的人类泵直向同源物。离子产生瞬态电流是在 30 多年前首次发现的。它们已在各种制剂中进行了研究，包括天然和异源表达系统。在这里，我们回顾了过去三年的工作，使用这些瞬态电信号来了解 Na+ 和 K+ 离子通过 Na+/K+-ATPase 运动的动力学转变，并提出这项工作可能对理解功能障碍的重要性负责一些新发现的神经病理学的人类泵直向同源物。