Ethidium bromide staining reveals rapid cell dispersion in the rat dentate gyrus following ouabain-induced injury

Omar, Ayman I.; Senatorov, Vladimir V.; Hu, Bin

doi:10.1016/s0306-4522(99)00398-x

Cited by 9 publications

(2 citation statements)

References 39 publications

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“…Similar nuclear morphology has previously been described in ouabain-treated cultured cortical neurons undergoing hybrid cell death47. Furthermore, similar hippocampal pathology has previously been reported in rats injected with ouabain into the hippocampus48 and in a rat model of pilocarpine-induced chronic epilepsy49, thus strengthening the link between Na + /K + -ATPases perturbations and seizure.…”

Section: Discussionsupporting

confidence: 81%

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

Holm

Isaksen

Glerup

et al. 2016

Sci Rep

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The Na+/K+-ATPases maintain Na+ and K+ electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na+/K+-ATPase α3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the α3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (α3+/D801Y) was generated. The α3+/D801Y mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the α3+/D801Y mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na+/K+-ATPase α3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission.

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Section: Discussionsupporting

confidence: 81%

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

Holm

Isaksen

Glerup

et al. 2016

Sci Rep

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“…The center of the quadrants is used as a reference for the mean Di-BAC 4 (3) fluorescence and forward scatter signal of control cells. et al, 1971;Watabe et al, 1996;Olej et al, 1998;Kawazoe et al, 1999;Stelmashook et al, 1999;McConkey et al, 2000;Omar, Senatorov & Hu, 2000;Chueh et al, 2001;Kurosawa et al, 2001;Hennion et al, 2002;Schmiedt et al, 2002;Xiao et al, 2002aXiao et al, , 2002bHuang et al, 2004;Esteves et al, 2005;Lang, Schulte & Schmiedt, 2005), or to enhance apoptosis induced by different stimuli in various model systems (Thevenod & Friedmann, 1999;Nobel et al, 2000;Penning et al, 2000;Verheye-Dua & Bohm, 2000;Bortner et al, 2001;Xiao et al, 2002a;Orlov et al, 2003;Esteves et al, 2005). Alterations in the expression and activity of the Na + -K + ATPase have also been widely reported to occur during the pathogenesis of cardiovascular, neurological, renal and metabolic diseases, as well as during heavy metalinduced toxicity (Patrick & Hilton, 1979;Lees, 1991;Rose & Valdes, 1994;Chauhan, Lee & Siegel, 1997;Mishra & Delivoria-Papadopoulos, 1999;Thevenod & Friedmann, 1999;Ziegelhoffer et al, 2000;Kumar & Kurup, 2002;Rodrigo et al, 2002;Yu, 2003a;Cimen et al, 2004).…”

Section: Sodium-potassium Pump (Namentioning

confidence: 99%

Potential Roles of Electrogenic Ion Transport and Plasma Membrane Depolarization in Apoptosis

2006

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Apoptosis is characterized by the programmed activation of specific biochemical pathways leading to the organized demise of cells. To date, aspects of the intracellular signaling machinery involved in this phenomenon have been extensively dissected and characterized. However, recent studies have elucidated a novel role for changes in the intracellular milieu of the cells as important modulators of the cell death program. Specially, intracellular ionic homeostasis has been reported to be a determinant in both the activation and progression of the apoptotic cascade. Several apoptotic insults trigger specific changes in ionic gradients across the plasma membrane leading to depolarization of the plasma membrane potential (PMP). These changes lead to ionic imbalance early during apoptosis. Several studies have also suggested the activation and/or modulation of specific ionic transport mechanisms including ion channels, transporters and ATPases, as mediators of altered intracellular ionic homeostasis leading to PMP depolarization during apoptosis. However, the role of PMP depolarization and of the changes in ionic homeostasis during the progression of apoptosis are still unclear. This review summarizes the current knowledge regarding the causes and consequences of PMP depolarization during apoptosis. We also review the potential electrogenic ion transport mechanisms associated with this event, including the net influx/efflux of cations and anions. An understanding of these mechamisms could lead to the generation of new therapeutic approaches for a variety of diseases involving apoptosis.

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Na+, K+-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death

2003

Biochemical Pharmacology

172

102

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Ethidium bromide staining reveals rapid cell dispersion in the rat dentate gyrus following ouabain-induced injury

Cited by 9 publications

References 39 publications

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

Potential Roles of Electrogenic Ion Transport and Plasma Membrane Depolarization in Apoptosis

Na+, K+-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death

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