Lack of Contribution of Mitochondrial Electron Transport to Acute O2 Sensing in Model Airway Chemoreceptors

Searle, Gavin J.; Hartness, Matthew E.; Hoareau, Rachel; Peers, Chris; Kemp, Paul J.

doi:10.1006/bbrc.2002.6428

Cited by 34 publications

(21 citation statements)

References 22 publications

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“…Further, the relevance of the mitochondrial respiratory chain as oxygen sensor was questioned in experiments with various cell lines defective in components of the electron-transport chain. These studies showed decreased H 2 O 2 levels under hypoxia and activation of HIF-1␣ with no difference in wild-type cells (27)(28)(29).…”

Section: Discussionmentioning

confidence: 88%

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Liu

Berchner‐Pfannschmidt

Möller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

157

113

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It has been proposed that hydroxyl radicals (⅐OH) generated in a perinuclear iron-dependent Fenton reaction are involved in O 2-dependent gene expression. Thus, it was the aim of this study to localize the cellular compartment in which the Fenton reaction takes place and to determine whether scavenging of ⅐OH can modulate hypoxia-inducible factor 1 (HIF-1)-dependent gene expression. The Fenton reaction was localized by using the nonfluorescent dihydrorhodamine (DHR) 123 that is irreversibly oxidized to fluorescent rhodamine 123 while scavenging ⅐OH together with gene constructs allowing fluorescent labeling of mitochondria, endoplasmic reticulum (ER), Golgi apparatus, peroxisomes, or lysosomes. A 3D two-photon confocal laser scanning microscopy showed ⅐OH generation in distinct hot spots of perinuclear ER pockets. This ER-based Fenton reaction was strictly pO 2-dependent.

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Section: Discussionmentioning

confidence: 88%

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Liu

Berchner‐Pfannschmidt

Möller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

157

113

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“…While it was reported that hypoxia caused mitochondrial depolarization in glomus cells (25) and the hypoxia responsiveness of intact glomus cells was reduced by rotenone, an inhibitor of complex I (158), other inhibitors of the mitochondrial electron transfer chain had no effect, suggesting that the action of rotenone may have been independent of its effects on the mitochondria. Moreover, the hypoxia-induced reduction of I K was maintained in airway chemoreceptor cells devoid of mitochondria or after mitochondrial inhibition (191).…”

Section: Chemoreceptorsmentioning

confidence: 95%

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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“…Hypoxia reduces the K ϩ conductance of neuroepithelial cells and releases vasoactive amines (e.g., serotonin), which contribute to the local vasomotor tone in the lung (and the optimization of ventilation-perfusion ratio), and also function as neurotransmitters for the afferent pathways to respiratory centers. In contrast to glomus cells, the primary target of hypoxia (with respect to the regulation of K ϩ conductance) is NADPH oxidase in this tissue, while the mitochondrial involvement is negligible (300). It has been suggested that NADPH oxidase maintains oxidizing environment required for tonic K ϩ channel activity, and this is abolished during hypoxia (257).…”

Section: Detection Of Hypoxia By Neuroepithelial Bodiesmentioning

confidence: 99%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

777

769

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Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K2P channel types) that this primary hyperpolarizing action is not performed passively. The K2P channels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K2P channel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K2P channel family into the spotlight. In this review, we focus on the physiological roles of K2P channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.

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Lack of Contribution of Mitochondrial Electron Transport to Acute O2 Sensing in Model Airway Chemoreceptors

Cited by 34 publications

References 22 publications

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Hypoxia. 4. Hypoxia and ion channel function

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

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Lack of Contribution of Mitochondrial Electron Transport to Acute O2 Sensing in Model Airway Chemoreceptors

Cited by 34 publications

References 22 publications

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Hypoxia. 4. Hypoxia and ion channel function

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

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Product

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Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels