Effect of Hypoxia/Ischemia on Voltage‐Dependent Channels

Gu, Xiang; Yao, Heng‐Chen; Haddad, Gabriel G.

doi:10.1002/9780470429907.ch9

Cited by 2 publications

(1 citation statement)

References 134 publications

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“…For example, we observed that after being exposed to prolonged hypoxia during postnatal development, cortical neurons are more sensitive to subsequent stress, which is largely attenuated by Na + channel blocker tetrodotoxin (TTX). Intriguingly, an increased Na + channel density/current (Gu and Haddad, 2003; Gu et al, 2008; Xia et al, 2000) and decreased DOR density (Xia et al, 2001) occurred in the exposed brain. Furthermore, we observed that in a mutant brain with epileptic seizures, cortical neurons are hyper-excitable with an up-regulation of voltage-gated Na + channels (Xia et al, 2003) and down-regulation of DOR expression (Zhao et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex

Chao¹,

He²,

Yang³

et al. 2012

Experimental Neurology

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Activation of delta-opioid receptors (DOR) is neuroprotective against hypoxic/ischemic injury in the cortex, which is at least partially related to its action against hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal injury. Na+ influx through TTX-sensitive voltage-gated Na+ channels may be a main mechanism for hypoxia-induced disruption of K+ homeostasis, with DOR activation attenuating the disruption of ionic homeostasis by targeting voltage-gated Na+ channels. In the present study we examined the role of DOR in the regulation of Na+ influx in anoxia and simulated ischemia (oxygen-glucose deprivation) as well as the effect of DOR activation on the Na+ influx induced by a Na+ channel opener without anoxic/ischemic stress and explored a potential PKC mechanism underlying the DOR action. We directly measured extracellular Na+ activity in mouse cortical slices with Na+ selective electrodes and found that (1) anoxia-induced Na+ influx occurred mainly through TTX-sensitive Na+ channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na+ influx; (3) veratridine, a Na+ channel opener, enhanced the anoxia-induced Na+ influx; this could be attenuated by DOR activation; (4) DOR activation did not reduce the anoxia-induced Na+ influx in the presence of chelerythrine, a broad-spectrum PKC blocker; and (5) DOR effects were blocked by PKCβII peptide inhibitor, and PKCθ pseudosubstrate inhibitor, respectively. We conclude that DOR activation inhibits anoxia-induced Na+ influx through Na+ channels via PKC (especially PKCβII and PKCθ isoforms) dependent mechanisms in the cortex.

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Section: Introductionmentioning

confidence: 99%

DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex

Chao¹,

He²,

Yang³

et al. 2012

Experimental Neurology

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Moderate Hypoxia Influences Potassium Outward Currents in Adipose-Derived Stem Cells

et al. 2014

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Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs) enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+) channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA) was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current-voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels.

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Effect of Hypoxia/Ischemia on Voltage‐Dependent Channels

Cited by 2 publications

References 134 publications

DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex

DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex

Moderate Hypoxia Influences Potassium Outward Currents in Adipose-Derived Stem Cells

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