Regulation of the human ether-a-gogo related gene (HERG) K<sup>+</sup>channels by reactive oxygen species

Taglialatela, Maurizio; Castaldo, Pasqualina; Iossa, Susanna; Pannaccione, Anna; Fresi, Angela; Ficker, Eckhard; Annunziato, Lucio

doi:10.1073/pnas.94.21.11698

Cited by 80 publications

(76 citation statements)

References 40 publications

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“…Previous studies have reported that functional properties of hERG channels are altered by RS [14][15][16][17]41]. However, different effects on hERG channel functions were shown for different RS.…”

Section: Discussionmentioning

confidence: 99%

“…However, different effects on hERG channel functions were shown for different RS. For example, experimental generation of RS using the iron/ascorbate reaction increases outward currents through hERG channels expressed in Xenopus oocytes [14]. The current enhancing effect requires two histidine residues at positions 578 and 587 in the S5-S6 linker region of the channel [17].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, auxiliary β-subunits of voltage-dependent K + channels also contain such RSsensitive cysteine residues, resulting in redox-dependent inactivation of the α-β-subunit channel complexes [13]. Similarly, functional properties of hERG1 channels also have been suggested to be altered by RS [14][15][16][17], potentially in a cysteine- [15] or a histidinedependent manner [17].…”

Section: Introductionmentioning

confidence: 99%

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Functional consequences of methionine oxidation of hERG potassium channels

Limberis

Martin

et al. 2007

Biochemical Pharmacology

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Reactive species oxidatively modify numerous proteins including ion channels. Oxidative sensitivity of ion channels is often conferred by amino acids containing sulfur atoms, such as cysteine and methionine. Functional consequences of oxidative modification of methionine in hERG1 (human ether à go-go related gene 1), which encodes cardiac I Kr channels, are unknown. Here we used chloramine-T (ChT), which preferentially oxidizes methionine, to examine the functional consequences of methionine oxidation of hERG channels stably expressed in a human embryonic kidney cell line (HEK 293) and native hERG channels in a human neuroblastoma cell line (SH-SY5Y). ChT (300 µM) significantly decreased whole-cell hERG current in both HEK 293 and SH-SY5Y cells. In HEK 293 cells, the effects of ChT on hERG current were time-and concentration-dependent, and were markedly attenuated in the presence of enzyme methionine sulfoxide reductase A that specifically repairs oxidized methionine. After treatment with ChT, the channel deactivation upon repolarization to −60 or −100 mV was significantly accelerated. The effect of ChT on channel activation kinetics was voltage-dependent; activation slowed during depolarization to +30 mV but accelerated during depolarization to 0 or −10 mV. In contrast, the reversal potential, inactivation kinetics, and voltage-dependence of steady-state inactivation remained unaltered. Our results demonstrate that the redox status of methionine is an important modulator of hERG channel.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional consequences of methionine oxidation of hERG potassium channels

Limberis

Martin

et al. 2007

Biochemical Pharmacology

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“…The oxidant H 2 O 2 or the thiol modifier MTSEA impairs the contribution of the RCK2 Ca 2 + bowl sensor, but not of the RCK1 sensor, to the overall Ca 2 + -dependent activation process of the channel. Mutation of C911 noticeably diminishes the propensity of Slo1 channels to rundown on patch excision (159) (127). The absence of a free SH/S -group at position 911 thus disrupts the normal function of the RCK2 Ca 2 + sensor and the Ca 2 + -dependent gating of the Slo1 channel.…”

Section: Functional Consequences Of Cysteine Oxidation In Slo1mentioning

confidence: 99%

“…Taglialatela et al (127) showed that ROS induced by iron/ ascorbate (Fe/asc) increased Kv11.1-mediated outward current in Xenopus oocytes while the inward current was not affected. This augmentation of Kv11.1 current by ROS was caused by a 12-mV right-shift of the steady-state inactivation.…”

Section: The Erg Groupmentioning

confidence: 99%

Oxidative Modulation of Voltage-Gated Potassium Channels

Sahoo

Hoshi

Heinemann

2014

Antioxidants & Redox Signaling

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Significance: Voltage-gated K + channels are a large family of K + -selective ion channel protein complexes that open on membrane depolarization. These K + channels are expressed in diverse tissues and their function is vital for numerous physiological processes, in particular of neurons and muscle cells. Potentially reversible oxidative regulation of voltage-gated K + channels by reactive species such as reactive oxygen species (ROS) represents a contributing mechanism of normal cellular plasticity and may play important roles in diverse pathologies including neurodegenerative diseases. Recent Advances: Studies using various protocols of oxidative modification, site-directed mutagenesis, and structural and kinetic modeling provide a broader phenomenology and emerging mechanistic insights. Critical Issues: Physicochemical mechanisms of the functional consequences of oxidative modifications of voltage-gated K + channels are only beginning to be revealed. In vivo documentation of oxidative modifications of specific amino-acid residues of various voltage-gated K + channel proteins, including the target specificity issue, is largely absent. Future Directions: High-resolution chemical and proteomic analysis of ion channel proteins with respect to oxidative modification combined with ongoing studies on channel structure and function will provide a better understanding of how the function of voltage-gated K + channels is tuned by ROS and the corresponding reducing enzymes to meet cellular needs. Antioxid. Redox Signal. 21, 933-952.

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Flow cytometric assessment of morphology, viability, and production of reactive oxygen species of Crassostrea gigas oocytes. Application to Toxic dinoflagellate (Alexandrium minutum) exposure

et al. 2014

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The Pacific oyster Crassostrea gigas accounts for a large part of shellfish aquaculture production worldwide. Aspects of morphological and functional characteristics of oyster oocytes remain poorly documented, and traditional techniques, such as microscopic observations of shape or fertilization rate, are time and space consuming. The purpose of this study was to assess for the first time viability and reactive oxygen species (ROS) production of Pacific oyster oocytes using flow cytometry (FCM) and to apply this method to determine oocyte responses to in vitro exposure to the toxic dinoflagellate Alexandrium minutum. A culture of A. minutum caused a significant increase in oocyte ROS production, which gradually increased with the age of the culture, but viability was not affected. Effect of the supernatant of the same A. minutum culture did not cause any significant modifications of oocyte morphology, viability, or ROS level. This study confirmed that some oocyte cellular characteristics can be assessed using FCM techniques. V C 2014 International Society for Advancement of Cytometry Key terms Pacific oyster; gamete quality; ROS production; viability; flow cytometry; ecotoxicology THE Pacific oyster Crassostrea gigas has considerable commercial value worldwide, including in France. Oyster seed production relies upon gamete quality, fertilization success, and larval development. As gamete quality is the first step in the spatproduction sequence, it is necessary to assess the quality of gametes in broodstock oysters first and foremost.To date, bioassays to assess oocyte quality are limited, and those available are tedious and time-consuming. Oocyte quality can be described using morphological characteristics by microscopy (1). Although microscope observations are unavoidable and useful to validate flow cytometry (FCM), assays based on microscope observations often have little predictive value and can be subjective according to each observer. Determinations of biochemical content (proteins, carbohydrates, and lipids) have been used as criteria of oocyte quality (2-4). More recently, proteomic profiles of oocytes were proposed as quality estimators (5,6). All of these biochemical assays, however, are fairly tedious to perform and provide only retrospective information. Fertilization rate, hatching rate, and larval development are used as complementary end points to evaluate oocyte quality (7-10); however, as these processes depend also upon spermatozoa quality, variability and inconsistency from one experiment to another often are encountered.

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Regulation of the human ether-a-gogo related gene (HERG) K⁺channels by reactive oxygen species

Cited by 80 publications

References 40 publications

Functional consequences of methionine oxidation of hERG potassium channels

Functional consequences of methionine oxidation of hERG potassium channels

Oxidative Modulation of Voltage-Gated Potassium Channels

Flow cytometric assessment of morphology, viability, and production of reactive oxygen species of Crassostrea gigas oocytes. Application to Toxic dinoflagellate (Alexandrium minutum) exposure

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Regulation of the human ether-a-gogo related gene (HERG) K+channels by reactive oxygen species

Cited by 80 publications

References 40 publications

Functional consequences of methionine oxidation of hERG potassium channels

Functional consequences of methionine oxidation of hERG potassium channels

Oxidative Modulation of Voltage-Gated Potassium Channels

Flow cytometric assessment of morphology, viability, and production of reactive oxygen species of Crassostrea gigas oocytes. Application to Toxic dinoflagellate (Alexandrium minutum) exposure

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Regulation of the human ether-a-gogo related gene (HERG) K⁺channels by reactive oxygen species