Cloning and functional expression of a rat heart KATP channel

M. L. J. Ashford, C. T. Bond, T. A. Blair, J. P. Adelman

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    168 Citations (Scopus)

    Abstract

    Potassium channels that are ATP-sensitive (KATP) couple membrane potential to the metabolic status of the cell. KATP channels are inhibited by intracellular ATP and are stimulated by intracellular nucleotide diphosphates. KATP channels are important regulators of secretory processes and muscle contraction, and are targets for therapeutic treatment of type II diabetes by the inhibitory sulphonylureas and for hypertension by activators such as pinacidil. In cardiac tissue, KATP channels are central regulators of post-ischaemic cardioprotection. Electrophysiological and pharmacological characteristics vary among KATP channels recorded from diverse tissues suggesting extensive molecular heterogeneity. A complementary DNA encoding a KATP channel was isolated from rat heart using the polymerase chain reaction. We report here that the expressed channels possess all of the essential features of native cardiac KATP channels, including sensitivity to intracellular nucleotides. In addition the cloned channels are activated by the potassium channel opener, pinacidil, but are not inhibited by the sulphonylurea, glibenclamide.
    Original languageEnglish
    Pages (from-to)456-459
    Number of pages4
    JournalNature
    Volume370
    Issue number6489
    DOIs
    Publication statusPublished - 1994

    Keywords

    • Glyburide
    • Pinacidil
    • Animals
    • Ion Channel Gating
    • Humans
    • Guanidines
    • Organ Specificity
    • Amino Acid Sequence
    • Potassium Channels
    • Cloning, Molecular
    • Rats
    • Polymerase Chain Reaction
    • Molecular Sequence Data
    • Membrane Potentials
    • Adenosine Triphosphate
    • Sequence Homology, Amino Acid
    • Cell Line
    • Cricetinae
    • Myocardium

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