Three methionine residues located within the regulator of conductance for K+ (RCK) domains confer oxidative sensitivity to large‐conductance Ca2+‐activated K+ channels

Santarelli, Lindsey Ciali; Wassef, Ramez; Heinemann, Stefan H.; Hoshi, Toshinori

doi:10.1113/jphysiol.2005.101089

Cited by 56 publications

(49 citation statements)

References 63 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Particularly in other ion channels, ChT does indeed act as a Met-preferring oxidizing agent as demonstrated by using electrophysiology and site-directed mutagenesis [20,23]. Substitution of critical Met residues with less readily oxidized residues, such as Leu, eliminates the ChT sensitivity [20,21,23]. Our observation that DTT does not diminish the ChT effect on hERG current (Fig.…”

Section: Discussionmentioning

confidence: 53%

“…Selective oxidation of methionine to MetO by ChT (< 10 mM) has been demonstrated in different proteins [33][34][35][36][37][38][39][40]. Particularly in other ion channels, ChT does indeed act as a Met-preferring oxidizing agent as demonstrated by using electrophysiology and site-directed mutagenesis [20,23]. Substitution of critical Met residues with less readily oxidized residues, such as Leu, eliminates the ChT sensitivity [20,21,23].…”

Section: Discussionmentioning

confidence: 99%

“…ChT at concentrations of ≤10 mM preferentially oxidizes Met to MetO in various proteins and MSRA can at least partially repair MetO to Met in the presence of DTT [23,24]. If the inhibition of hERG current (Figs.…”

Section: Effects Of Cht On Herg K + Currentmentioning

confidence: 99%

“…Oxidation of a single Met residue in the S6 segment near the channel pore also alters a distinct inactivation process, P/C-type inactivation, in ShB channels [21]. Another K + channel robustly regulated by Met oxidation is the large-conductance Ca 2+ -activated K + channel, in which oxidation of specific Met residues in the cytosolic C-terminal domain dramatically increases the channel activity [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…Thus we investigated if these K + channels undergo functional changes in response to treatments that promote Met oxidation. We used chloramine-T (ChT) as a Met-preferring oxidant [20][21][22][23][24] and studied its effect on recombinant hERG1 channels expressed in mammalian cells with and without recombinant bovine MSRA in the cytosolic solution. We report here that Met oxidation potently inhibits hERG1 channels and that exogenous MSRA protects the channels against the oxidative damage.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Functional consequences of methionine oxidation of hERG potassium channels

Limberis

Martin

et al. 2007

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Cht On Herg K + Currentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional consequences of methionine oxidation of hERG potassium channels

Limberis

Martin

et al. 2007

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

Effect of Individual Fc Methionine Oxidation on FcRn Binding: Met252 Oxidation Impairs FcRn Binding More Profoundly than Met428 Oxidation

Gao¹,

Ji²,

Veeravalli

et al. 2015

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Redox signalling in cardiovascular disease

Charles

Eaton

2008

Proteomics Clinical Apps

View full text Add to dashboard Cite

Oxidative stress has almost universally and unequivocally been implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress in cells and cardiovascular biology was once considered only in terms of injury, disease and dysfunction. However, it is now appreciated that oxidants are also produced in healthy tissues, and they function as signalling molecules transmitting information throughout the cell. Conversely, when cells move to a more reduced state, as can occur when oxygen is limiting, this can also result in alterations in the function of biomolecules and subsequently cells. At the centre of this 'redox signalling' are oxidoreductive chemical reactions involving oxidants or reductants post translationally modifying proteins. These structural alterations allow changes in cellular redox state to be coupled to alterations in cell function. In this review, we consider aspects of redox signalling in the cardiovascular system, focusing on the molecular basis of redox sensing by proteins and the array of post-translational oxidative modifications that can occur. In addition, we discuss studies utilising proteomic methods to identify redox-sensitive cardiac proteins, as well as those using this technology more broadly to assess redox signalling in cardiovascular disease.

show abstract

Three methionine residues located within the regulator of conductance for K⁺ (RCK) domains confer oxidative sensitivity to large‐conductance Ca²⁺‐activated K⁺ channels

Cited by 56 publications

References 63 publications

Functional consequences of methionine oxidation of hERG potassium channels

Functional consequences of methionine oxidation of hERG potassium channels

Effect of Individual Fc Methionine Oxidation on FcRn Binding: Met252 Oxidation Impairs FcRn Binding More Profoundly than Met428 Oxidation

Redox signalling in cardiovascular disease

Contact Info

Product

Resources

About