Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel
J Neurosci. 2019 Jul 10;39(28):5440-5451. doi: 10.1523/JNEUROSCI.0265-19.2019. Epub 2019 May 13.
The Na/K-ATPase (NKA) is a ubiquitous membrane-bound enzyme responsible for generating and maintaining the Na and K electrochemical gradients across the plasmalemma of living cells. Numerous studies in non-neuronal tissues have shown that this transport mechanism is reversibly regulated by phosphorylation/dephosphorylation of the catalytic α subunit and/or associated proteins. In neurons, Na/K transport by NKA is essential for almost all neuronal operations, consuming up to two-thirds of the neuron's energy expenditure. However, little is known about its cellular regulatory mechanisms. Here we have used an electrophysiological approach to monitor NKA transport activity in male rat hippocampal neurons We report that this activity is regulated by a balance between serine/threonine phosphorylation and dephosphorylation. Phosphorylation by the protein kinases PKG and PKC inhibits NKA activity, whereas dephosphorylation by the protein phosphatases PP-1 and PP-2B (calcineurin) reverses this effect. Given that these kinases and phosphatases serve as downstream effectors in key neuronal signaling pathways, they may mediate the coupling of primary messengers, such as neurotransmitters, hormones, and growth factors, to the NKAs, through which multiple brain functions can be regulated or dysregulated. The Na/K-ATPase (NKA), known as the "Na pump," is a ubiquitous membrane-bound enzyme responsible for generating and maintaining the Na and K electrochemical gradients across the plasma membrane of living cells. In neurons, as in most types of cells, the NKA generates the negative resting membrane potential, which is the basis for almost all aspects of cellular function. Here we used an electrophysiological approach to monitor physiological NKA transport activity in single hippocampal pyramidal cells We have found that neuronal NKA activity is oppositely regulated by phosphorylation and dephosphorylation, and we have identified the main protein kinases and phosphatases mediating this regulation. This fundamental form of NKA regulation likely plays a role in multiple brain functions.
钠钾-ATP 酶（NKA）是一种普遍存在的膜结合酶，负责在活细胞的质膜两侧产生和维持钠和钾电化学梯度。大量非神经组织的研究表明，这种转运机制可通过磷酸化/去磷酸化催化α亚基和/或相关蛋白而被可逆调节。在神经元中，NKA 介导的钠钾转运对几乎所有神经元活动都是必不可少的，其消耗了神经元能量支出的三分之二以上。然而，其细胞调节机制知之甚少。在此，我们使用电生理学方法监测雄性大鼠海马神经元中的 NKA 转运活性。我们报告称，该活性受丝氨酸/苏氨酸磷酸化和去磷酸化之间的平衡调节。蛋白激酶 PKG 和 PKC 的磷酸化抑制 NKA 活性，而蛋白磷酸酶 PP-1 和 PP-2B（钙调神经磷酸酶）的去磷酸化则逆转了这种效应。鉴于这些激酶和磷酸酶作为关键神经元信号通路的下游效应物，它们可能介导包括神经递质、激素和生长因子在内的初级信使与 NKA 的偶联，从而调节或失调多种脑功能。钠钾-ATP 酶（NKA），又名“钠泵”，是一种普遍存在的膜结合酶，负责在活细胞的质膜两侧产生和维持钠和钾电化学梯度。在神经元中，与大多数类型的细胞一样，NKA 产生负的静息膜电位，这是几乎所有细胞功能的基础。在此，我们使用电生理学方法监测单个海马锥体神经元中的生理 NKA 转运活性。我们发现神经元 NKA 活性受磷酸化和去磷酸化的相反调节，并鉴定了介导这种调节的主要蛋白激酶和磷酸酶。这种基本形式的 NKA 调节可能在多种脑功能中发挥作用。
