Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells

Emfinger, Christopher H.; Welscher, Alecia; Yan, Zihan; Wang, Yixi; Conway, Herbert; Moss, Jane; Moss, Larry G.; Remedi, Marı́a S.; Nichols, Colin G.

doi:10.1098/rsos.160808

Cited by 16 publications

(38 citation statements)

References 52 publications

(84 reference statements)

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“…; Emfinger et al. ), with higher peak blood glucose and slower return to baseline glucose after a glucose injection.…”

Section: Discussionmentioning

confidence: 99%

“…Mammalian and Danio K ATP genes are very similar (>90% identity at the amino acid level) (Emfinger et al. ). K ATP ‐GOF zebrafish, expressing the identical transgene that we originally used in mice (Koster et al.…”

Section: Discussionmentioning

confidence: 99%

“…Previously described protocols were used to isolate islet (Emfinger et al. ) and brain (Lopez‐Ramirez et al. ) tissues.…”

Section: Methodsmentioning

confidence: 99%

“…Whole‐cell voltage clamp recordings of K currents and excised inside‐out patch‐clamp recording of K ATP currents was also carried out as previously described (Emfinger et al. ). In all experiments, pipette resistance was typically 2–3 MΩ, data were filtered at 1 kHz and recorded at 3 kHz.…”

Section: Methodsmentioning

confidence: 99%

“…This is important, both from an evolutionary perspective, and to provide novel insights to the process. We have recently shown that K ATP channels are expressed in b-cells within the zebrafish (Danio rerio) islet, that they are functionally similar to their mammalian orthologs, and that activation of these channels by the drug diazoxide can similarly alter glucose tolerance (Emfinger et al 2017). Previous studies have suggested a role for K ATP channels in early islet responses to overnutrition: activation of K ATP , either pharmacologically or with inducible transgenes, increases b-cell growth in response to excess nutrients (Li et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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Beta‐cell excitability and excitability‐driven diabetes in adult Zebrafish islets

et al. 2019

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Islet β ‐cell membrane excitability is a well‐established regulator of mammalian insulin secretion, and defects in β ‐cell excitability are linked to multiple forms of diabetes. Evolutionary conservation of islet excitability in lower organisms is largely unexplored. Here we show that adult zebrafish islet calcium levels rise in response to elevated extracellular [glucose], with similar concentration–response relationship to mammalian β ‐cells. However, zebrafish islet calcium transients are nor well coupled, with a shallower glucose‐dependence of cytoplasmic calcium concentration. We have also generated transgenic zebrafish that conditionally express gain‐of‐function mutations in ATP‐sensitive K + channels (K ATP ‐GOF) in β ‐cells. Following induction, these fish become profoundly diabetic, paralleling features of mammalian diabetes resulting from equivalent mutations. K ATP ‐GOF fish become severely hyperglycemic, with slowed growth, and their islets lose glucose‐induced calcium responses. These results indicate that, although lacking tight cell‐cell coupling of intracellular Ca 2+ , adult zebrafish islets recapitulate similar excitability‐driven β ‐cell glucose responsiveness to those in mammals, and exhibit profound susceptibility to diabetes as a result of inexcitability. While illustrating evolutionary conservation of islet excitability in lower vertebrates, these results also provide important validation of zebrafish as a suitable animal model in which to identify modulators of islet excitability and diabetes.

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“…; Emfinger et al. ), with higher peak blood glucose and slower return to baseline glucose after a glucose injection.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Previously described protocols were used to isolate islet (Emfinger et al. ) and brain (Lopez‐Ramirez et al. ) tissues.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Beta‐cell excitability and excitability‐driven diabetes in adult Zebrafish islets

et al. 2019

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ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Tinker

Aziz

et al. 2018

Comprehensive Physiology

111

112

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ATP sensitive potassium channels (K ) are so named because they open as cellular ATP levels fall. This leads to membrane hyperpolarization and thus links cellular metabolism to membrane excitability. They also respond to MgADP and are regulated by a number of cell signaling pathways. They have a rich and diverse pharmacology with a number of agents acting as specific inhibitors and activators. K channels are formed of pore-forming subunits, Kir6.1 and Kir6.2, and a large auxiliary subunit, the sulfonylurea receptor (SUR1, SUR2A, and SUR2B). The Kir6.0 subunits are a member of the inwardly rectifying family of potassium channels and the sulfonylurea receptor is part of the ATP-binding cassette family of proteins. Four SURs and four Kir6.x form an octameric channel complex and the association of a particular SUR with a specific Kir6.x subunit constitutes the K current in a particular tissue. A combination of mutagenesis work combined with structural studies has identified how these channels work as molecular machines. They have a variety of physiological roles including controlling the release of insulin from pancreatic β cells and regulating blood vessel tone and blood pressure. Furthermore, mutations in the genes underlie human diseases such as congenital diabetes and hyperinsulinism. Additionally, opening of these channels is protective in a number of pathological conditions such as myocardial ischemia and stroke. © 2018 American Physiological Society. Compr Physiol 8:1463-1511, 2018.

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Evolution of inwardly rectifying potassium channels and their gene expression in zebrafish embryos

Silic

Murata

Park

et al. 2021

Developmental Dynamics

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Background Inwardly rectifying potassium channels are essential for normal potassium homeostasis, maintaining the cellular resting membrane potential, and regulating electrolyte transportation. Mutations in Kir channels have been known to cause debilitating diseases ranging from neurological abnormalities to renal and cardiac failures. Many efforts have been made to understand their protein structures, physiological functions, and pharmacological modifiers. However, their expression and functions during embryonic development remain largely unknown. Results Using zebrafish as a model, we identified and renamed 31 kir genes. We also analyzed Kir gene evolution by phylogenetic and syntenic analyses. Our data indicated that the four subtypes of the Kir genes might have already evolved out in chordates. These vertebrate Kir genes most likely resulted from both whole‐genome duplications and tandem duplications. In addition, we examined zebrafish kir gene expression during early embryogenesis. Each subgroup's genes showed similar but distinct gene expression domains. The gene expression of ohnologous genes from teleost‐specific whole‐genome duplication indicated subfunctionalization. Varied temporal gene expression domains suggest that Kir channels may be needed for embryonic patterning or regulation. Conclusions Our phylogenetic and developmental analyses of Kir channels shed light on their evolutionary history and potential functions during embryogenesis related to congenital diseases and human channelopathies.

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Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells

Cited by 16 publications

References 52 publications

Beta‐cell excitability and excitability‐driven diabetes in adult Zebrafish islets

Beta‐cell excitability and excitability‐driven diabetes in adult Zebrafish islets

ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Evolution of inwardly rectifying potassium channels and their gene expression in zebrafish embryos

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