Domain Organization of the ATP-sensitive Potassium Channel Complex Examined by Fluorescence Resonance Energy Transfer

Wang, Shizhen; Makhina, Elena; Masia, Ricard; Hyrc, Krzysztof L.; Formanack, Mary Lynn; Nichols, Colin G.

doi:10.1074/jbc.m112.388629

Cited by 10 publications

(5 citation statements)

References 40 publications

(67 reference statements)

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“…1B) 20 . How the Kir6 and SUR subunits are physically connected remains unknown, but electron micrography and intersubunit FRET studies of complete K ATP complexes suggest an intimate packing of 4 SUR and 4 Kir6.x subunits 21,22 (Fig. 1A).…”

Section: Katp Channel Structure and Molecular Regulationmentioning

confidence: 99%

K _ATP Channels and Cardiovascular Disease

Nichols

Singh

Grange

2013

Circulation Research

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ATP-sensitive potassium (KATP ) channels were first discovered in the heart 30 years ago1. Reconstitution of KATP channel activity by coexpression of members of the pore-forming inward rectifier gene family (Kir6.1, KCNJ8, and Kir6.2 KCNJ11) with sulfonylurea receptors (SUR1, ABCC8, and SUR2, ABCC9) of the ABCC protein sub-family, has led to the elucidation of many details of channel gating and pore properties. In addition, the essential roles of Kir6.x and SURx subunits in generating cardiac and vascular KATP2 and the detrimental consequences of genetic deletions or mutations in mice have been recognised3. However, despite this extensive body of knowledge, there has been a paucity of defined roles of KATP subunits in human cardiovascular diseases, although there are reports of association of a single Kir6.1 variant with the J-wave syndrome in the electrocardiogram, and two isolated studies have reported association of loss of function mutations in SUR2 with atrial fibrillation and heart failure. Two new studies convincingly demonstrate that mutations in the SUR2 gene are associated with Cantu syndrome, a complex multi-organ disorder characterized by hypertrichosis, craniofacial dysmorphology, osteochondrodysplasia, patent ductus arteriosus, cardiomegaly, pericardial effusion, and lymphoedema. As we discuss, this realization of previously unconsidered consequences provides significant insight into the roles of the KATP channel in the cardiovascular system and suggests novel therapeutic possibilities.

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Section: Katp Channel Structure and Molecular Regulationmentioning

confidence: 99%

K _ATP Channels and Cardiovascular Disease

Nichols

Singh

Grange

2013

Circulation Research

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150

104

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“…In multimeric channels with arbitrary subunit assembly, the total apparent FRET efficiency can be calculated from a binomial distribution, from which the real FRET efficiency can be derived. For example, this strategy has been used to investigate the relative arrangement of SUR1 and Kir 6.2 in K ATP channels [105] and the assembly of heteromeric TRP channels [48]. …”

Section: Biological Applications Of Fretmentioning

confidence: 99%

Application of fluorescence resonance energy transfer in protein studies

Yang

Zheng

2014

Journal of Molecular Structure

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Since the physical process of fluorescence resonance energy transfer (FRET) was elucidated more than six decades ago, this peculiar fluorescence phenomenon has turned into a powerful tool for biomedical research due to its compatibility in scale with biological molecules as well as rapid developments in novel fluorophores and optical detection techniques. A wide variety of FRET approaches have been devised, each with its own advantages and drawbacks. Especially in the last decade or so, we are witnessing a flourish of FRET applications in biological investigations, many of which exemplify clever experimental design and rigorous analysis. Here we review the current stage of FRET methods development with the main focus on its applications in protein studies in biological systems, by summarizing the basic components of FRET techniques, most established quantification methods, as well as potential pitfalls, illustrated by example applications.

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“…The activity of K ATP channel is affected by the concentration of intracellular ATP/ADP ( 16 ). Previous findings have shown that Kir subunit had binding sites of ATP ( 17 ), with the most effective endogenous blocker being achieved through ATP ligand activity but not Mg 2+ . ADP and other nucleoside diphosphates serve as endogenous agonists to K + channel ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Cytomembrane ATP-sensitive K+ channels in neurovascular unit targets of ischemic stroke in the recovery period

Yang

Pan

Zheng

et al. 2016

Experimental and Therapeutic Medicine

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The present study was to analyze the mechanism of cytomembrane ATP-sensitive K+ channels (KATP) in the neurovascular unit treatment of ischemic stroke in the recovery period. A total of 24 healthy adult male Wistar rats of 5–8 weeks age, weighing 160–200 g were randomly divided into the control (sham-operation group), model, KATP blocker and KATP opener groups (n=6 rats per group). Nylon cerebral artery occlusion was conducted using nylon monofilament coated with Poly-L-lysine, which was used to produce a cerebral infarction model. After feeding normally for 3 days, 5-hydroxydecanoate (40 mg/Kg), and diazoxide (40 mg/Kg) were injected to the abdominal cavity in the blocker, and opener groups, respectively. The control received an equivalent normal saline that was injected into the sham-operation and model groups. The animals were mutilated and samples were collected after 3 days. RT-PCR was used to detect the expression levels of the three subunits of KATP, i.e., kir6.1, and sulfonylurea receptor (SUR) 1 and SUR2 mRNA, as well as to calculate infarct size in tetrazolium chloride staining. The expression level of mRNA in the opener group were significantly higher, followed by the model and blocker groups, with the control group being the lowest (P<0.05). Infarct size in the opener group was markedly smaller than the model and blocker groups, and infarct size in the blocker group was significantly larger (P<0.05). Thus, the target treatment on KATP may improve the prognosis of ischemic stroke during the recovery period.

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Domain Organization of the ATP-sensitive Potassium Channel Complex Examined by Fluorescence Resonance Energy Transfer

Cited by 10 publications

References 40 publications

K _ATP Channels and Cardiovascular Disease

K _ATP Channels and Cardiovascular Disease

Application of fluorescence resonance energy transfer in protein studies

Cytomembrane ATP-sensitive K+ channels in neurovascular unit targets of ischemic stroke in the recovery period

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Domain Organization of the ATP-sensitive Potassium Channel Complex Examined by Fluorescence Resonance Energy Transfer

Cited by 10 publications

References 40 publications

K ATP Channels and Cardiovascular Disease

K ATP Channels and Cardiovascular Disease

Application of fluorescence resonance energy transfer in protein studies

Cytomembrane ATP-sensitive K+ channels in neurovascular unit targets of ischemic stroke in the recovery period

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Product

Resources

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K _ATP Channels and Cardiovascular Disease

K _ATP Channels and Cardiovascular Disease