Department of Physiology and Neurobiology and Program in Experimental and Molecular Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
J Neurosci. 2013 Aug 7;33(32):13025-41. doi: 10.1523/JNEUROSCI.0220-13.2013.
The sodium-potassium ATPase (i.e., the "sodium pump") plays a central role in maintaining ionic homeostasis in all cells. Although the sodium pump is intrinsically electrogenic and responsive to dynamic changes in intracellular sodium concentration, its role in regulating neuronal excitability remains unclear. Here we describe a physiological role for the sodium pump in regulating the excitability of mouse neocortical layer 5 and hippocampal CA1 pyramidal neurons. Trains of action potentials produced long-lasting (∼20 s) afterhyperpolarizations (AHPs) that were insensitive to blockade of voltage-gated calcium channels or chelation of intracellular calcium, but were blocked by tetrodotoxin, ouabain, or the removal of extracellular potassium. Correspondingly, the AHP time course was similar to the decay of activity-induced increases in intracellular sodium, whereas intracellular calcium decayed at much faster rates. To determine whether physiological patterns of activity engage the sodium pump, we replayed in vitro a place-specific burst of 15 action potentials recorded originally in vivo in a CA1 "place cell" as the animal traversed the associated place field. In both layer 5 and CA1 pyramidal neurons, this "place cell train" generated small, long-lasting AHPs capable of reducing neuronal excitability for many seconds. Place-cell-train-induced AHPs were blocked by ouabain or removal of extracellular potassium, but not by intracellular calcium chelation. Finally, we found calcium contributions to the AHP to be temperature dependent: prominent at room temperature, but largely absent at 35°C. Our results demonstrate a previously unappreciated role for the sodium-potassium ATPase in regulating the excitability of neocortical and hippocampal pyramidal neurons.
钠钾 ATP 酶（即“钠泵”）在维持所有细胞中的离子动态平衡方面起着核心作用。尽管钠泵本质上是电生成的，并对细胞内钠离子浓度的动态变化做出反应，但它在调节神经元兴奋性方面的作用仍不清楚。在这里，我们描述了钠泵在调节小鼠新皮层 5 层和海马 CA1 锥体神经元兴奋性方面的生理作用。动作电位的串可产生持续时间较长（约 20 秒）的后超极化（AHP），该超极化对电压门控钙通道阻断或细胞内钙螯合不敏感，但对河豚毒素、哇巴因或细胞外钾去除敏感。相应地，AHP 的时间过程与活性诱导的细胞内钠离子增加的衰减相似，而细胞内钙离子的衰减速度要快得多。为了确定生理活动模式是否会激活钠泵，我们在体外重现了最初在体内记录的 CA1“位置细胞”中特定位置的 15 个动作电位的爆发，当动物穿过相关位置场时。在 5 层和 CA1 锥体神经元中，这种“位置细胞串”产生的小、长时 AHP 能够降低神经元兴奋性数秒。哇巴因或细胞外钾去除可阻断位置细胞串诱导的 AHP，但细胞内钙螯合不能阻断。最后，我们发现钙对 AHP 的贡献取决于温度：在室温下很明显，但在 35°C 时基本不存在。我们的研究结果表明，钠钾 ATP 酶在调节新皮层和海马锥体神经元兴奋性方面发挥了以前未被认识到的作用。
