Sulfhydryl oxidation induces rapid and reversible closure of the ATP‐regulated K<sup>+</sup> channel in the pancreatic β‐cell

Islam, Shahidul; Berggren, Per Olof; Larsson, Olof

doi:10.1016/0014-5793(93)80051-u

Cited by 76 publications

(52 citation statements)

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“…5,6,9) However, an additional factor may also be involved in this antiarrhythmia. Various studies have shown that both thimerosal [15][16][17] and pinacidil 32,33) induce coronary vasodilation.…”

Section: Discussionmentioning

confidence: 99%

“…2) ATP-sensitive K + channels (K-ATP channels) in skeletal muscle, 3,4) heart lines [6][7][8] are closed by thiol-oxidizing reagents, an effect that is in general reversed by the disulphide bond reducing agent 1,4-dithiothreitol (DTT). This modulation of K-ATP channel activity by thiol oxidation is of particular interest in heart and skeletal muscle.…”

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confidence: 99%

“…18) Thimerosal decreases the sensitivity of the ATP dependent potassium channel to ATP 5) and leads to the blockage of the channel. 6) The opening of the channel by the ATP dependent potassium channel opener analog P1075 was blocked by thimerosal. 19) The involvement of opening or closing of the ATP dependent potassium channel and the mechanism to decrease myocardial ischemic or reperfusion induced damage or development of arrhythmias have been studied.…”

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Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

et al. 2005

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SUMMARYThiol-modifying agents induce the release of nitric oxide (NO) from endothelial epithelium and the release of reactive oxygen free radicals in the vascular system. Moreover, thiol groups are essential for the functioning of the ATP dependent potassium channel (K-ATP). The effects of thiol-modifying agents and their molecular mechanisms on arrhythmia have not been widely studied. In this study, we investigated the effect of the hydrophilic SH-group-oxidizing substance thimerosal on the arrhythmia induced by reperfusion/ischemia after coronary artery ligation in rats. We studied the possible involvement of the K-ATP and NOS on the effect of thimerosal. Thimerosal pretreatment (3, 30 mg/kg dose iv. 10 minutes before coronary occlusion) significantly decreased the length of total arrhythmia, ventricular tachycardia, and the arrhythmia score. This effect of thimerosal was reversed by the K-ATP opener pinacidil but not by the K-ATP blocker glibenclamide. The inhibition of iNOS by L-NAME did not alter the antiarrhythmic effect of thimerosal. These data clearly suggest that the antiarrhythmic effect of thimerosal is dependent upon the blockage of K-ATP. ( 1) The activity of some K + channels is drastically altered by the oxidation of critical SH-groups of the channel protein. An interesting example is the loss of rapid inactivation of the voltage-gated K + channel RCK4 (Kv1.4) produced by oxidation of a thiol group; this residue is located near the intracellular inactivation (ball) domain of the channel.2) ATP-sensitive K + channels (K-ATP channels) in skeletal muscle, 3,4) heart 5) and pancreatic β-cells or insulin-secreting cellFrom the

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Section: Discussionmentioning

confidence: 99%

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Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

et al. 2005

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“…Although the mechanism by which PN alters ATPsensitive channels is not understood [82,154], it is unlikely that the oxidant properties of PN are involved since oxidants have been shown to reduce ATP-sensitive potassium channel activity [206,207]. Moreover, PN mediate vasodilator responses have been shown to be markedly attenuated by the ATP-sensitive potassium channel blocker, glibenclamide [208], but are not attenuated by L-penicillamine, in doses that can reduce the vasodilator responses to L-Snitrosocysteine, a S-nitrosothiol [163].…”

Section: Vasorelaxant Properties Of Peroxyni-tritementioning

confidence: 99%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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“…This process effectively protects the cell from oxidative damage. Typically, GSSG is then converted to GSH via glutathione reductase or effluxed from the cell and degraded by extracellular-glutamyl transpeptidase [14,15] . The oxidation state and intracellular concentration of glutathione are therefore useful indicators of oxidative stress in cells.…”

Section: Introductionmentioning

confidence: 99%

Modulation of KATP currents in rat ventricular myocytes by hypoxia and a redox reaction

Yan

Zhang

2009

Acta Pharmacol Sin

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Aim: The present study investigated the possible regulatory mechanisms of redox agents and hypoxia on the K ATP current (I KATP ) in acutely isolated rat ventricular myocytes. Methods: Single-channel and whole-cell patch-clamp techniques were used to record the K ATP current (I KATP ) in acutely isolated rat ventricular myocytes. Results: Oxidized glutathione (GSSG, 1 mmol/L) increased the I KATP , while reduced glutathione (GSH, 1 mmol/L) could reverse the increased I KATP during normoxia. To further corroborate the effect of the redox agent on the K ATP channel, we employed the redox couple DTT (1 mmol/L)/H 2 O 2 (0.3, 0.6, and 1 mmol/L) and repeated the previous processes, which produced results similar to the previous redox couple GSH/GSSG during normoxia. H 2 O 2 increased the I KATP in a concentration dependent manner, which was reversed by DTT (1 mmol/L). In addition, our results have shown that 15 min of hypoxia increased the I KATP , while GSH (1 mmol/L) could reverse the increased I KATP . Furthermore, in order to study the signaling pathways of the I KATP augmented by hypoxia and the redox agent, we applied a protein kinase C(PKC) inhibitor bisindolylmaleimide VI (BIM), a protein kinase G(PKG) inhibitor KT5823, a protein kinase A (PKA) inhibitor H-89, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitors KN-62 and KN-93. The results indicated that BIM, KT5823, KN-62, and KN-93, but not H-89, inhibited the I KATP augmented by hypoxia and GSSG; in addition, these results suggest that the effects of both GSSG and hypoxia on K ATP channels involve the activation of the PKC, PKG, and CaMK II pathways, but not the PKA pathway. Conclusion: The present study provides electrophysiological evidence that hypoxia and the oxidizing reaction are closely related to the modulation of I KATP .

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Sulfhydryl oxidation induces rapid and reversible closure of the ATP‐regulated K⁺ channel in the pancreatic β‐cell

Abstract: Effects of sulfhydryl modification on the ATP regulated K' channel (K,,, channel) in the pancreatic B-cell were studied, using the patch clamp technique. Application of the sulfhydryl oxidizing agents thimerosal and [ 18,191.

Cited by 76 publications

References 40 publications

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

Potential Benefits of Peroxynitrite

Modulation of KATP currents in rat ventricular myocytes by hypoxia and a redox reaction

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Sulfhydryl oxidation induces rapid and reversible closure of the ATP‐regulated K+ channel in the pancreatic β‐cell

Abstract: Effects of sulfhydryl modification on the ATP regulated K' channel (K,,, channel) in the pancreatic B-cell were studied, using the patch clamp technique. Application of the sulfhydryl oxidizing agents thimerosal and [ 18,191.

Cited by 76 publications

References 40 publications

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

Potential Benefits of Peroxynitrite

Modulation of KATP currents in rat ventricular myocytes by hypoxia and a redox reaction

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Sulfhydryl oxidation induces rapid and reversible closure of the ATP‐regulated K⁺ channel in the pancreatic β‐cell