The cytoplasmic C-terminus of the sulfonylurea receptor is important for KATP channel function but is not key for complex assembly or trafficking

Authors

  • Jonathan P. Giblin,

    1. Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, UK
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    • Note: These authors contributed equally to this work

  • Kathryn Quinn,

    1. Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, UK
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    • Note: These authors contributed equally to this work

  • Andrew Tinker

    1. Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, UK
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A. Tinker, Room F2, 4th Floor, Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK, Fax: + 44 20 76912838, Tel.: + 44 20 76796192, E-mail: a.tinker@ucl.ac.uk

Abstract

ATP-sensitive K+ channels are an octameric assembly of two proteins, a sulfonylurea receptor (SUR1) and an ion conducting subunit (Kir 6.0). We have examined the role of the C-terminus of SUR1 by expressing a series of truncation mutants together with Kir6.2 stably in HEK293 cells. Biochemical analyses using coimmunoprecipitation indicate that SUR1 deletion mutants and Kir6.2 assemble and that a SUR1 deletion mutant binds glibenclamide with high affinity. Electrophysiological recordings indicate that ATP sensitivity is normal but the response of the mutant channel complexes to tolbutamide, MgADP and diazoxide is disturbed. Quantitative immunofluorescence and cell surface biotinylation supports the idea that there is little disturbance in the efficiency of trafficking. Our data show that deletions of the C-terminal most cytoplasmic domain of SUR1, can result in functional channels at the plasma membrane in mammalian cells that have an abnormal response to physiological and pharmacological agents.

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