Pharmacological and molecular docking studies reveal that glibenclamide competitively inhibits diazoxide-induced mitochondrial ATP-sensitive potassium channel activation and pharmacological preconditioning

Palácio, Plínio Bezerra; Lucas, Aline Maria Brito; Alexandre, Joana Varlla de Lacerda; Cunha, Pedro Lourenzo Oliveira; Viana, Yuana Ivia Ponte; Albuquerque, Amanda Cabral; Varela, Anna Lídia Nunes; Facundo, Heberty T.

doi:10.1016/j.ejphar.2021.174379

Cited by 6 publications

(2 citation statements)

References 27 publications

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“…These K ATP channels are formed by Kir6.2 and regulatory sulfonylurea receptor (SUR) subunits, which bind diazoxide [ 49 ]. The cardioprotective properties of diazoxide have also been reported [ 28 ] and are thought to be associated with its binding to mitoSUR subunits of mitoK ATP channels [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of a Recombinant Mitochondrial ROMK2 Potassium Channel Expressed in Bacteria and Reconstituted in Planar Lipid Bilayers

et al. 2023

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In the inner mitochondrial membrane, several potassium channels that play a role in cell life and death have been identified. One of these channels is the ATP-regulated potassium channel (mitoKATP). The ROMK2 potassium channel is a potential molecular component of the mitoKATP channel. The current study aimed to investigate the pharmacological modulation of the activity of the ROMK2 potassium channel expressed in Escherichia coli bacteria. ROMK2 was solubilized in polymer nanodiscs and incorporated in planar lipid bilayers. The impact of known mitoKATP channel modulators on the activity of the ROMK2 was characterized. We found that the ROMK2 channel was activated by the mitoKATP channel opener diazoxide and blocked by mitoKATP inhibitors such as ATP/Mg2+, 5-hydroxydecanoic acid, and antidiabetic sulfonylurea glibenclamide. These results indicate that the ROMK2 potassium protein may be a pore-forming subunit of mitoKATP and that the impact of channel modulators is not related to the presence of accessory proteins.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of a Recombinant Mitochondrial ROMK2 Potassium Channel Expressed in Bacteria and Reconstituted in Planar Lipid Bilayers

et al. 2023

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“…mitoK ATP channels are involved in a series of physiological and pathophysiological changes to mitigate cardiomyocyte injury and apoptosis. mitoK ATP channels have been described as being located in the inner mitochondrial membrane and they have protective properties for ischemic myocardium; moreover, their existence has been the subject of heated debate ( Bezerra Palácio et al, 2021 ). Recently, the molecular composition of mitoK ATP was shown by Paggio et al, and they are comprised of pore-forming (MITOK, encoded by the CCDC51 gene (NCBI ID 79714)) and regulatory (MITOSUR, tissue expression correlates with ABCB8) subunits ( Paggio et al, 2019 ) ( Figure 2 ).…”

Section: K Atp Channels In Cardiovascular Diseasesmentioning

confidence: 99%

Functional Regulation of KATP Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

et al. 2022

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ATP-sensitive potassium channels (KATP channels) play pivotal roles in excitable cells and link cellular metabolism with membrane excitability. The action potential converts electricity into dynamics by ion channel-mediated ion exchange to generate systole, involved in every heartbeat. Activation of the KATP channel repolarizes the membrane potential and decreases early afterdepolarization (EAD)-mediated arrhythmias. KATP channels in cardiomyocytes have less function under physiological conditions but they open during severe and prolonged anoxia due to a reduced ATP/ADP ratio, lessening cellular excitability and thus preventing action potential generation and cell contraction. Small active molecules activate and enhance the opening of the KATP channel, which induces the repolarization of the membrane and decreases the occurrence of malignant arrhythmia. Accumulated evidence indicates that mutation of KATP channels deteriorates the regulatory roles in mutation-related diseases. However, patients with mutations in KATP channels still have no efficient treatment. Hence, in this study, we describe the role of KATP channels and subunits in angiocardiopathy, summarize the mutations of the KATP channels and the functional regulation of small active molecules in KATP channels, elucidate the potential mechanisms of mutant KATP channels and provide insight into clinical therapeutic strategies.

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The role of sulfonylureas in the treatment of type 2 diabetes

Tomlinson

Patil

Fok

et al. 2021

Expert Opinion on Pharmacotherapy

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Pharmacological and molecular docking studies reveal that glibenclamide competitively inhibits diazoxide-induced mitochondrial ATP-sensitive potassium channel activation and pharmacological preconditioning

Cited by 6 publications

References 27 publications

Pharmacological Characterization of a Recombinant Mitochondrial ROMK2 Potassium Channel Expressed in Bacteria and Reconstituted in Planar Lipid Bilayers

Pharmacological Characterization of a Recombinant Mitochondrial ROMK2 Potassium Channel Expressed in Bacteria and Reconstituted in Planar Lipid Bilayers

Functional Regulation of KATP Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

The role of sulfonylureas in the treatment of type 2 diabetes

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