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Methods for Characterizing Disease-Associated ATP-Sensitive Potassium Channel Mutations

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Potassium Channels

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1684))

Abstract

The ATP-sensitive potassium (KATP) channel formed by the inwardly rectifying potassium channel Kir6.2 and the sulfonylurea receptor 1 (SUR1) plays a key role in regulating insulin secretion. Genetic mutations in KCNJ11 or ABCC8 which encode Kir6.2 and SUR1 respectively are major causes of insulin secretion disorders: those causing loss of channel function lead to congenital hyperinsulinism, whereas those causing gain of channel function result in neonatal diabetes and in some cases developmental delay, epilepsy, and neonatal diabetes, referred to as the DEND syndrome. Understanding how disease mutations disrupt channel expression and function is important for disease diagnosis and for devising effective therapeutic strategies. Here, we describe a workflow including several biochemical and functional assays to assess the effects of mutations on channel expression and function.

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Acknowledgments

This work was supported by National Institutes of Health grants R01DK057699 and R01DK066485 to S.L.S.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code L224, Portland, OR, 97239, USA

    Balamurugan Kandasamy

  2. Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code L224, Portland, OR, 97239, USA

    Show-Ling Shyng

Authors
  1. Balamurugan Kandasamy
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  2. Show-Ling Shyng
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Corresponding author

Correspondence to Show-Ling Shyng .

Editor information

Editors and Affiliations

  1. Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, USA

    Show-Ling Shyng

  2. Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, USA

    Francis I. Valiyaveetil

  3. The Vollum Institute, Oregon Health and Science University, Portland, Oregon, USA

    Matt Whorton

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Kandasamy, B., Shyng, SL. (2018). Methods for Characterizing Disease-Associated ATP-Sensitive Potassium Channel Mutations. In: Shyng, SL., Valiyaveetil, F., Whorton, M. (eds) Potassium Channels. Methods in Molecular Biology, vol 1684. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7362-0_8

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  • DOI: https://doi.org/10.1007/978-1-4939-7362-0_8

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7361-3

  • Online ISBN: 978-1-4939-7362-0

  • eBook Packages: Springer Protocols

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