Cloning and functional expression of a rat heart KATP channel

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

    Research output: Contribution to journalArticle

    167 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

    Fingerprint

    KATP Channels
    Organism Cloning
    Pinacidil
    Nucleotides
    Glyburide
    Diphosphates
    Secretory Pathway
    Potassium Channels
    Muscle Contraction
    Membrane Potentials
    Type 2 Diabetes Mellitus
    Complementary DNA
    Adenosine Triphosphate
    Pharmacology
    Hypertension
    Polymerase Chain Reaction
    Therapeutics

    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

    Cite this

    Ashford, M. L. J., Bond, C. T., Blair, T. A., & Adelman, J. P. (1994). Cloning and functional expression of a rat heart KATP channel. Nature, 370(6489), 456-459. https://doi.org/10.1038/370456a0
    Ashford, M. L. J. ; Bond, C. T. ; Blair, T. A. ; Adelman, J. P. / Cloning and functional expression of a rat heart KATP channel. In: Nature. 1994 ; Vol. 370, No. 6489. pp. 456-459.
    @article{e4bc871b11174e6f9bde8dbeb26bcbb9,
    title = "Cloning and functional expression of a rat heart KATP channel",
    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.",
    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",
    author = "Ashford, {M. L. J.} and Bond, {C. T.} and Blair, {T. A.} and Adelman, {J. P.}",
    year = "1994",
    doi = "10.1038/370456a0",
    language = "English",
    volume = "370",
    pages = "456--459",
    journal = "Nature",
    issn = "0028-0836",
    publisher = "Nature Publishing Group",
    number = "6489",

    }

    Ashford, MLJ, Bond, CT, Blair, TA & Adelman, JP 1994, 'Cloning and functional expression of a rat heart KATP channel', Nature, vol. 370, no. 6489, pp. 456-459. https://doi.org/10.1038/370456a0

    Cloning and functional expression of a rat heart KATP channel. / Ashford, M. L. J.; Bond, C. T.; Blair, T. A.; Adelman, J. P.

    In: Nature, Vol. 370, No. 6489, 1994, p. 456-459.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Cloning and functional expression of a rat heart KATP channel

    AU - Ashford, M. L. J.

    AU - Bond, C. T.

    AU - Blair, T. A.

    AU - Adelman, J. P.

    PY - 1994

    Y1 - 1994

    N2 - 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.

    AB - 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.

    KW - Glyburide

    KW - Pinacidil

    KW - Animals

    KW - Ion Channel Gating

    KW - Humans

    KW - Guanidines

    KW - Organ Specificity

    KW - Amino Acid Sequence

    KW - Potassium Channels

    KW - Cloning, Molecular

    KW - Rats

    KW - Polymerase Chain Reaction

    KW - Molecular Sequence Data

    KW - Membrane Potentials

    KW - Adenosine Triphosphate

    KW - Sequence Homology, Amino Acid

    KW - Cell Line

    KW - Cricetinae

    KW - Myocardium

    U2 - 10.1038/370456a0

    DO - 10.1038/370456a0

    M3 - Article

    VL - 370

    SP - 456

    EP - 459

    JO - Nature

    JF - Nature

    SN - 0028-0836

    IS - 6489

    ER -