Different neuronal Na⁺/K⁺‐ATPase isoforms are involved in diverse signaling pathways

Abstract

Inhibition of rat neuronal Na(+)/K(+)-ATPase alpha3 isoform at low (100 nM) ouabain concentration led to activation of MAP kinase cascade via PKC and PIP(3) kinase. In contrast to ouabain-sensitive alpha3 isoform of Na(+)/K(+)-ATPase, an ouabain-resistant alpha1 isoform (inhibition with 1 mM of ouabain) of Na(+)/K(+)-ATPase regulates MAP kinase via Src kinase dependent reactions. Using of Annexin V-FITC apoptotic test to determine the cells with early apoptotic features allows to conclude that alpha3 isoform stimulates and alpha1 suppresses apoptotic process in cerebellum neurons. These data are the first demonstration showing participation of ouabain-resistant (alpha1) and ouabain-sensitive (alpha3) Na(+)/K(+)-ATPase isoforms in diverse signaling pathways in neuronal cells.

Na+/K+-pump and neurotransmitter membrane receptors

“…The Na + /K + -pump is an active transporter that uses ATP hydrolysis as an energy source to move both ions across the neuronal membrane against their concentration gradients and has specific functions associated with the generation of the action potential, as well as with the maintenance of other active transport mechanisms, regulation of the cell volume (Karpova et al 2010a, b) and heat generation (Clarke et al 2013). This current review is primarily concerned with studies on the Na + /K + -pump in neurons and its role in the regulation of transmitter receptors but will first provide an overview of its cellular functions.…”

Pinealon Increases Cell Viability by Suppression of Free Radical Levels and Activating Proliferative Processes

“…As shown earlier, incubation of neurons with a specific inhibitor of Na/K-ATPase ouabain results in accumulation of free radicals and activation of ERK 1/2 kinase, 14 which induces switching on of the so-called early response genes. 18 Incubation of DCF-DA pre-loaded rat cerebellum granule cells with 100 nM ouabain causes an increase in their fluorescence, which is a sign of increasing intracellular levels of free radicals (Fig.…”

“…Ouabain affects sodium/potassium-adenosine triphosphatase (Na/K-ATPase) of the outer cell membrane. 13,14 HC is a congener of N-methyl-D-aspartate (NMDA), and it acts via the glutamate receptor of the NMDA class. 15 In both cases, an increase in intracellular ROS levels and activation of the key enzyme of the mitogen-activated protein kinase (MAPK) cascade ERK1/2 kinase (extracellular regulated kinase, isoforms 1 and 2) is observed.…”

“…15 In both cases, an increase in intracellular ROS levels and activation of the key enzyme of the mitogen-activated protein kinase (MAPK) cascade ERK1/2 kinase (extracellular regulated kinase, isoforms 1 and 2) is observed. 14,15 Each ligand was used in a concentration sufficient to induce oxidative stress via intracellular accumulation of ROS. 14,15 The cell suspension was incubated with ouabain or HC (in the presence or absence of pinealon), and then flow cytometry analysis was performed.…”

“…14,15 Each ligand was used in a concentration sufficient to induce oxidative stress via intracellular accumulation of ROS. 14,15 The cell suspension was incubated with ouabain or HC (in the presence or absence of pinealon), and then flow cytometry analysis was performed.…”