Modification of the Mitochondrial Sulfonylurea Receptor by Thiol Reagents

Szewczyk, Adam; Wójcik, Grażyna; Lobanov, Nikolai A.; Nałȩcz, Maciej J.

doi:10.1006/bbrc.1999.1190

Cited by 22 publications

(13 citation statements)

References 31 publications

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“…The underlying mechanism for a difference in the effect of NADH vs. NADPH, despite their identical redox potentials, is elusive at this stage. Interestingly, while both surface K ATP channels [42-45] and the mK ATP [12,13,18,46,47] do have redox active thiols, NADPH does not directly reduce thiols, suggesting its direct redox activity is not the mechanism of channel regulation.…”

Section: Resultsmentioning

confidence: 99%

Redox regulation of the mitochondrial KATP channel in cardioprotection

Queliconi

Wojtovich

Nadtochiy

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The mitochondrial ATP-sensitive potassium channel (mKATP) is important in the protective mechanism of ischemic preconditioning (IPC). The channel is reportedly sensitive to reactive oxygen and nitrogen species, and the aim of this study was to compare such species in parallel, to build a more comprehensive picture of mKATP regulation. mKATP activity was measured by both osmotic swelling and Tl+ flux assays, in isolated rat heart mitochondria. An isolated adult rat cardiomyocyte model of ischemia-reperfusion (IR) injury was also used to determine the role of mKATP in cardioprotection by nitroxyl. Key findings were as follows: (i) mKATP was activated by O2•- and H2O2 but not other peroxides. (ii) mKATP was inhibited by NADPH. (iii) mKATP was activated by S-nitrosothiols, nitroxyl, and nitrolinoleate. The latter two species also inhibited mitochondrial complex II. (iv) Nitroxyl protected cardiomyocytes against IR injury in a mKATP-dependent manner. Overall, these results suggest that the mKATP channel is activated by specific reactive oxygen and nitrogen species, and inhibited by NADPH. The redox modulation of mKATP may be an underlying mechanism for its regulation in the context of IPC.

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Section: Resultsmentioning

confidence: 99%

Redox regulation of the mitochondrial KATP channel in cardioprotection

Queliconi

Wojtovich

Nadtochiy

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Second, magnesium reduced the inhibitory potency of glibenclamide to block the cardiac mitoK ATP channel [3]. Third, it was shown that Mg 2+ caused also an increase in the total and specific binding of [ 3 H]glibenclamide to the inner mitochondrial membrane [19].…”

Section: Discussionmentioning

confidence: 99%

Matrix Mg²⁺ regulates mitochondrial ATP‐dependent potassium channel from heart

2005

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Mitochondrial ATP-regulated potassium (mitoK ATP ) channels play an important role in cardioprotection. Single channel activity was measured after reconstitution of inner mitochondrial membranes from bovine myocardium into a planar lipid bilayer. After incorporation, the potassium channel was recorded with a mean conductance of 103 ± 9 pS. The channel activity was inhibited by ATP/Mg and activated by GDP. Magnesium ions alone affected, in a dose dependent manner, both the channel conductance and the open probability. Magnesium ions regulated the mitoK ATP channel only when added to the trans compartment. We conclude that Mg 2+ regulates the cardiac mitoK ATP channel from the matrix site by affecting both the channel conductance and gating.

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“…The oxidant DTNB dose-dependently inhibited cardiomyocyte K ATP channels through oxidation of the thiol groups of these channels, in particular in the sulfonylurea receptor part (Coetzee et al 1995;Szewczyk et al 1999). In addition, K ATP channel susceptibility to oxidation increased with age, since lower DTNB doses inhibited K ATP channel activity in cardiomyocytes from the 24-month old animals.…”

Section: Discussionmentioning

confidence: 99%

Nicorandil protects ATP-sensitive potassium channels against oxidation-induced dysfunction in cardiomyocytes of aging rats

2008

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ATP-sensitive potassium channels (K(ATP) channels) regulate vascular tone and cardiac contraction through their action on the membrane potential of smooth muscle cells and cardiomyocytes. Because aging and diseases alter K(ATP) channel activity, many pharmacological treatments aimed at improving their function, therefore cardiovascular function, have been evaluated. Nicorandil, a K(ATP) channel opener, nitric oxide donor and antioxidant, is used as a treatment of angina pectoris and induces vasodilation, blood pressure decrease and cardioprotection in aging as well as after ischemia-reperfusion. Here, using the patch-clamp technique, we have studied the effect a chronic low dose of nicorandil (0.1 mg/kg per day for 2 months), on the activity of cardiomyocyte K(ATP) channels as a function of age, in newborn, 4-, 12- and 24-month old rats. Nicorandil exerted an anti-oxidant and protective action on cardiomyocyte K(ATP) channels, especially in aged animals, leading to restoration of a normal channel activity. These findings could justify further therapeutical applications.

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Modification of the Mitochondrial Sulfonylurea Receptor by Thiol Reagents

Cited by 22 publications

References 31 publications

Redox regulation of the mitochondrial KATP channel in cardioprotection

Redox regulation of the mitochondrial KATP channel in cardioprotection

Matrix Mg²⁺ regulates mitochondrial ATP‐dependent potassium channel from heart

Nicorandil protects ATP-sensitive potassium channels against oxidation-induced dysfunction in cardiomyocytes of aging rats

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Modification of the Mitochondrial Sulfonylurea Receptor by Thiol Reagents

Cited by 22 publications

References 31 publications

Redox regulation of the mitochondrial KATP channel in cardioprotection

Redox regulation of the mitochondrial KATP channel in cardioprotection

Matrix Mg2+ regulates mitochondrial ATP‐dependent potassium channel from heart

Nicorandil protects ATP-sensitive potassium channels against oxidation-induced dysfunction in cardiomyocytes of aging rats

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Matrix Mg²⁺ regulates mitochondrial ATP‐dependent potassium channel from heart