Expression of voltage-activated calcium channels in the early zebrafish embryo

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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“…; Sanhueza et al. ; Tarifeño‐Saldivia et al. ), but functional demonstration of Ca 2+ channels in fish islet cells is lacking.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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“…As developing muscle has been reported to have Ca v channels capable of supporting a Ca ++ -based action potential [12], these could be targets of high dose tricaine. The cacna1sa channel thought to be a muscle-specific subunit of the DHPR is expressed in zebrafish somitic muscle [40]. So high dose tricaine might block excitation-contraction coupling directly.…”

Section: Discussionmentioning

confidence: 99%

“…Ca v channels have similarities to Na v channels, in that their alpha subunits have clear structural and functional similarities [39]. Zebrafish somites make the first skeletal muscle and express L-type voltage gated calcium channels cacna1sa (CaV1.1)[40]. In contrast, the P/Q-type cacna1a is expressed in brain, neuronal cells and heart [40].…”

Section: Introductionmentioning

confidence: 99%

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Anaesthetic Tricaine Acts Preferentially on Neural Voltage-Gated Sodium Channels and Fails to Block Directly Evoked Muscle Contraction

Attili

Hughes

2014

PLoS ONE

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Movements in animals arise through concerted action of neurons and skeletal muscle. General anaesthetics prevent movement and cause loss of consciousness by blocking neural function. Anaesthetics of the amino amide-class are thought to act by blockade of voltage-gated sodium channels. In fish, the commonly used anaesthetic tricaine methanesulphonate, also known as 3-aminobenzoic acid ethyl ester, metacaine or MS-222, causes loss of consciousness. However, its role in blocking action potentials in distinct excitable cells is unclear, raising the possibility that tricaine could act as a neuromuscular blocking agent directly causing paralysis. Here we use evoked electrical stimulation to show that tricaine efficiently blocks neural action potentials, but does not prevent directly evoked muscle contraction. Nifedipine-sensitive L-type Cav channels affecting movement are also primarily neural, suggesting that muscle Nav channels are relatively insensitive to tricaine. These findings show that tricaine used at standard concentrations in zebrafish larvae does not paralyse muscle, thereby diminishing concern that a direct action on muscle could mask a lack of general anaesthesia.

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“…Although the exposure of embryos to pharmacological blockers of Ca 21 channels did not perturb early development, late effects were observed, suggesting that these channels may have a role in Ca 21 homeostasis and control of cellular processes during early embryonic development (Sanhueza et al, 2009). Very recent studies addressing the link between Ca 21 signaling, cleavage, differentiation, and growth showed the expression and functionality of the transient receptor potential melastatin 4 protein (TRPM4), and suggested the role of TRPM4-like channel in Ca 21 regulation during early development of the zebrafish (Cheng et al, 2015).…”

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confidence: 93%

Ion currents in embryo development

Tosti

Boni

Gallo

2016

Birth Defects Research Pt C

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Ion channels are proteins expressed in the plasma membrane of electrogenic cells. In the zygote and blastomeres of the developing embryo, electrical modifications result from ion currents that flow through these channels. This phenomenon implies that ion current activity exerts a specific developmental function, and plays a crucial role in signal transduction and the control of embryogenesis, from the early cleavage stages and during growth and development of the embryo. This review describes the involvement of ion currents in early embryo development, from marine invertebrates to human, focusing on the occurrence, modulation, and dynamic role of ion fluxes taking place on the zygote and blastomere plasma membrane, and at the intercellular communication between embryo cell stages.Birth Defects Research (Part C) 108:6-18, 2016.V C 2016 Wiley Periodicals, Inc.

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Expression of voltage-activated calcium channels in the early zebrafish embryo

Cited by 19 publications

References 18 publications

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

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

Anaesthetic Tricaine Acts Preferentially on Neural Voltage-Gated Sodium Channels and Fails to Block Directly Evoked Muscle Contraction

Ion currents in embryo development

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