Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sheldon, Claire A.; Diarra, Abdoullah; Cheng, Yen May; Church, John A.

doi:10.1523/jneurosci.2829-04.2004

Cited by 43 publications

(56 citation statements)

References 85 publications

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“…This cascade provides a new mechanistic explanation for the permissive role of Na þ in epithelial cell necrosis 17,18 and lengthens the growing list of Na þ toxicity mechanisms (Sheldon et al 19 and references therein). This mechanism differs from that in textbooks, 20 which pose the Ca 2 þ overload downstream of reversed NCX or activated VOCCs.…”

Section: Discussionmentioning

confidence: 88%

“…lower free energy). For this reason, we have used the term 'ATP steal' for the 19,31 Owing to its inhibition of glycolysis and oxidative phosphorylation plus activation of ATP usage by poly (ADP ribose) polymerase, hydrogen peroxide causes severe ATP depletion. 3,[32][33][34] A role for the Na þ /K þ ATPase as a significant ATP sink in H 2 O 2 -exposed cells was previously discarded in endothelial cells based on the failure of ouabain to rescue the ATP depletion.…”

Section: Discussionmentioning

confidence: 99%

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ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload

et al. 2006

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload

et al. 2006

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“…First, H ϩ translocation at the growth cone could promote the formation of subplasmalemmal alkaline and/or extracellular acidic microdomains to regulate, respectively, actin cytoskeletal dynamics and the strength of the cell-substrate adhesions required to support neurite outgrowth. Na ϩ /H ϩ exchange also promotes Na ϩ and, via reverse Na ϩ /Ca 2ϩ exchange, Ca 2ϩ influx (Sheldon et al, 2004;Luo et al, 2005), with additional potential effects on neurite outgrowth (Brackenbury et al, 2008). Second, functioning in parallel with other ion transporters, NHE1 could promote a net gain of NaCl and water entry, leading to localized swelling at the growth cone that could supply sufficient force to drive membrane protrusion.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Early Neurite Morphogenesis by the Na+/H+ Exchanger NHE1

Sin¹,

Moniz²,

Ozog³

et al. 2009

Journal of Neuroscience

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The ubiquitously expressed Na ϩ /H ϩ exchanger NHE1 plays an important role in regulating polarized membrane protrusion and directional motility in non-neuronal cells. Using NGF-differentiated PC12 cells and murine neocortical neurons in vitro, we now show that NHE1 plays a role in regulating early neurite morphogenesis. NHE1 was expressed in growth cones in which it gave rise to an elevated intracellular pH in actively extending neurites. The NHE1 inhibitor cariporide reversibly reduced growth cone filopodia number and the formation and elongation of neurites, especially branches, whereas the transient overexpression of full-length NHE1, but not NHE1 mutants deficient in either ion translocation activity or actin cytoskeletal anchoring, elicited opposite effects. In addition, compared with neocortical neurons obtained from wild-type littermates, neurons isolated from NHE1-null mice exhibited reductions in early neurite outgrowth, an effect that was rescued by overexpression of full-length NHE1 but not NHE1 mutants. Finally, the growth-promoting effects of netrin-1, but not BDNF or IGF-1, were markedly reduced by cariporide in wild-type neocortical neurons and were not observed in NHE1-null neurons. Although netrin-1 failed to increase growth cone intracellular pH or Na ϩ /H ϩ exchange activity, netrin-1-induced increases in early neurite outgrowth were restored in NHE1-null neurons transfected with full-length NHE1 but not an ion translocation-deficient mutant. Collectively, the results indicate that NHE1 participates in the regulation of early neurite morphogenesis and identify a novel role for NHE1 in the promotion of early neurite outgrowth by netrin-1.

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“…Voltage-gated Na ϩ channels are also present in neurons, and blockade of these channels attenuated depolarization and cell injury in response to anoxia/hypoxia (16, 184), suggesting that hypoxia activates these channels. Na ϩ influx may also occur through NSCCs, since Na ϩ influx induced by anoxia can be attenuated by blockade of NSCCs (194).…”

Section: Central Nervous Systemmentioning

confidence: 99%

Hypoxia. 4. Hypoxia and ion channel function

Shimoda

Polàk

2011

American Journal of Physiology-Cell Physiology

100

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The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. oxygen deprivation; mammalian ion channels; oxygen homeostasis SENSING and appropriately responding to changes in O 2 concentration is of paramount importance for the survival of all organisms. Over time, O 2 homeostasis has evolved into a complex system to regulate O 2 delivery and use. While the rapid response to acute reductions in O 2 concentration typically results from processes that alter preexisting proteins, such as phosphorylation, stabilization, dimerization, or degradation, durable adaptation to prolonged hypoxic insult requires a coordinated response at the level of gene transcription. Since a deficit in O 2 is an important component of various physiological processes and the pathogenesis of numerous diseases, understanding the mechanisms by which changes in O 2 are linked to cell function is of great interest.Ion channels play a critical role in regulating a wide variety of biological processes, including neuronal transmission; control of ventillation; contraction of cardiac, skeletal, and smooth muscle; transport of nutrients and ions across the epithelium; T-cell activation; and glucose metabolism and pancreatic ␤-cell insulin release. To date, over 300 types of ion channels, differing in their mode of activation (voltage-dependent or -independent, ligand-gated, mechanosensitive, pH) and their ionic permeability (K ϩ , Ca 2ϩ , Cl Ϫ , Na ϩ ), have been identified. This heterogeneity in ion channel populations provides an astonishing array of variable responses within and between cell types. In 1988, a report demonstrating that rabbit carotid body glomus cells express an O 2 -sensitive potassium channel ushered in a new era of research exploring whether ion channel activity could be regulated in response to changes in O 2 availability (131). Since that initial description of an O 2 -regulated ion channel, an abundance of work has been produced indicating that a variety of ion channels spread across the different ion channel families are O 2 sensitive and exhibit changes in channel activity with acute hypoxia and alterations in channel quantity with prolonged hypoxic challenge. Although a great amount of work has been devoted to the study of hypoxia and ion channels in reptiles, amp...

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Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Cited by 43 publications

References 85 publications

ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload

ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload

Regulation of Early Neurite Morphogenesis by the Na+/H+ Exchanger NHE1

Hypoxia. 4. Hypoxia and ion channel function

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