Extracellular cations modulate the ATP sensitivity of ATP-K$^{+}$ channels in rat ventromedial hypothalamic neurons

J. M. Treherne, M. L. J. Ashford

    Research output: Contribution to journalArticle

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    Abstract

    ATP-sensitive K$^{+}$ (ATP-K$^{+}$) channels underlie the glucose-sensing nature of pancreatic $\beta $-cells by way of their inhibition by intracellular ATP. Recently it has been proposed that ATP-K$^{+}$ channels have a similar function in certain hypothalamic neurons that become excitable in raised concentrations of extracellular glucose. The aim of this study was to assess the ATP sensitivity of ATP-K$^{+}$ channels in inside-out membrane patches excised from glucose-sensing neurons that were acutely isolated from the ventromedial nucleus of rat hypothalamus. ATP-K$^{+}$ channels were less sensitive to ATP in neurons than in other tissues. Moreover, the sensitivity of neuronal ATP-K$^{+}$ channels to inhibition by intracellular ATP was modulated by extracellular cations. Under physiological ionic gradients (i.e. high extracellular Na$^{+}$ and low K$^{+}$), intracellular ATP produced a concentration-dependent inhibition of channel activity, with a half-maximal inhibition (K$_{\text{i}}$) of 2.32 mM. A non-hydrolysable analogue of ATP, AMP(PNP), was similarly effective. In symmetrical K$^{+}$ (i.e. no extracellular sodium), channel activity was tenfold more sensitive to ATP (K$_{\text{i}}$ of 0.21 mM). A parallel study on ATP-K$^{+}$ channels from an insulin-secreting $\beta $-cell line (CRI-G1) showed that, in contrast to the neuronal data, extracellular cations had no effect on the ATP sensitivity of the channel.

    Original languageEnglish
    Pages (from-to)121-124
    Number of pages4
    JournalProceedings of the Royal Society B
    Volume247
    Issue number1319
    DOIs
    Publication statusPublished - 22 Feb 1992

    Fingerprint

    potassium channels
    Neurons
    Cations
    Rats
    cations
    Adenosine Triphosphate
    cation
    neurons
    rats
    glucose
    sodium channels
    islets of Langerhans
    hypothalamus
    Insulin-Secreting Cells
    Glucose
    insulin
    cell lines
    Adenylyl Imidodiphosphate
    Sodium Channels
    sodium

    Keywords

    • Sodium
    • Rats
    • Animals
    • Ventromedial Hypothalamic Nucleus
    • Potassium
    • Drug Resistance
    • Islets of Langerhans
    • Adenosine Triphosphate
    • Potassium Channels
    • Cell Line

    Cite this

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    title = "Extracellular cations modulate the ATP sensitivity of ATP-K$^{+}$ channels in rat ventromedial hypothalamic neurons",
    abstract = "ATP-sensitive K$^{+}$ (ATP-K$^{+}$) channels underlie the glucose-sensing nature of pancreatic $\beta $-cells by way of their inhibition by intracellular ATP. Recently it has been proposed that ATP-K$^{+}$ channels have a similar function in certain hypothalamic neurons that become excitable in raised concentrations of extracellular glucose. The aim of this study was to assess the ATP sensitivity of ATP-K$^{+}$ channels in inside-out membrane patches excised from glucose-sensing neurons that were acutely isolated from the ventromedial nucleus of rat hypothalamus. ATP-K$^{+}$ channels were less sensitive to ATP in neurons than in other tissues. Moreover, the sensitivity of neuronal ATP-K$^{+}$ channels to inhibition by intracellular ATP was modulated by extracellular cations. Under physiological ionic gradients (i.e. high extracellular Na$^{+}$ and low K$^{+}$), intracellular ATP produced a concentration-dependent inhibition of channel activity, with a half-maximal inhibition (K$_{\text{i}}$) of 2.32 mM. A non-hydrolysable analogue of ATP, AMP(PNP), was similarly effective. In symmetrical K$^{+}$ (i.e. no extracellular sodium), channel activity was tenfold more sensitive to ATP (K$_{\text{i}}$ of 0.21 mM). A parallel study on ATP-K$^{+}$ channels from an insulin-secreting $\beta $-cell line (CRI-G1) showed that, in contrast to the neuronal data, extracellular cations had no effect on the ATP sensitivity of the channel.",
    keywords = "Sodium, Rats, Animals, Ventromedial Hypothalamic Nucleus, Potassium, Drug Resistance, Islets of Langerhans, Adenosine Triphosphate, Potassium Channels, Cell Line",
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    Extracellular cations modulate the ATP sensitivity of ATP-K$^{+}$ channels in rat ventromedial hypothalamic neurons. / Treherne, J. M.; Ashford, M. L. J.

    In: Proceedings of the Royal Society B, Vol. 247, No. 1319, 22.02.1992, p. 121-124.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Extracellular cations modulate the ATP sensitivity of ATP-K$^{+}$ channels in rat ventromedial hypothalamic neurons

    AU - Treherne, J. M.

    AU - Ashford, M. L. J.

    PY - 1992/2/22

    Y1 - 1992/2/22

    N2 - ATP-sensitive K$^{+}$ (ATP-K$^{+}$) channels underlie the glucose-sensing nature of pancreatic $\beta $-cells by way of their inhibition by intracellular ATP. Recently it has been proposed that ATP-K$^{+}$ channels have a similar function in certain hypothalamic neurons that become excitable in raised concentrations of extracellular glucose. The aim of this study was to assess the ATP sensitivity of ATP-K$^{+}$ channels in inside-out membrane patches excised from glucose-sensing neurons that were acutely isolated from the ventromedial nucleus of rat hypothalamus. ATP-K$^{+}$ channels were less sensitive to ATP in neurons than in other tissues. Moreover, the sensitivity of neuronal ATP-K$^{+}$ channels to inhibition by intracellular ATP was modulated by extracellular cations. Under physiological ionic gradients (i.e. high extracellular Na$^{+}$ and low K$^{+}$), intracellular ATP produced a concentration-dependent inhibition of channel activity, with a half-maximal inhibition (K$_{\text{i}}$) of 2.32 mM. A non-hydrolysable analogue of ATP, AMP(PNP), was similarly effective. In symmetrical K$^{+}$ (i.e. no extracellular sodium), channel activity was tenfold more sensitive to ATP (K$_{\text{i}}$ of 0.21 mM). A parallel study on ATP-K$^{+}$ channels from an insulin-secreting $\beta $-cell line (CRI-G1) showed that, in contrast to the neuronal data, extracellular cations had no effect on the ATP sensitivity of the channel.

    AB - ATP-sensitive K$^{+}$ (ATP-K$^{+}$) channels underlie the glucose-sensing nature of pancreatic $\beta $-cells by way of their inhibition by intracellular ATP. Recently it has been proposed that ATP-K$^{+}$ channels have a similar function in certain hypothalamic neurons that become excitable in raised concentrations of extracellular glucose. The aim of this study was to assess the ATP sensitivity of ATP-K$^{+}$ channels in inside-out membrane patches excised from glucose-sensing neurons that were acutely isolated from the ventromedial nucleus of rat hypothalamus. ATP-K$^{+}$ channels were less sensitive to ATP in neurons than in other tissues. Moreover, the sensitivity of neuronal ATP-K$^{+}$ channels to inhibition by intracellular ATP was modulated by extracellular cations. Under physiological ionic gradients (i.e. high extracellular Na$^{+}$ and low K$^{+}$), intracellular ATP produced a concentration-dependent inhibition of channel activity, with a half-maximal inhibition (K$_{\text{i}}$) of 2.32 mM. A non-hydrolysable analogue of ATP, AMP(PNP), was similarly effective. In symmetrical K$^{+}$ (i.e. no extracellular sodium), channel activity was tenfold more sensitive to ATP (K$_{\text{i}}$ of 0.21 mM). A parallel study on ATP-K$^{+}$ channels from an insulin-secreting $\beta $-cell line (CRI-G1) showed that, in contrast to the neuronal data, extracellular cations had no effect on the ATP sensitivity of the channel.

    KW - Sodium

    KW - Rats

    KW - Animals

    KW - Ventromedial Hypothalamic Nucleus

    KW - Potassium

    KW - Drug Resistance

    KW - Islets of Langerhans

    KW - Adenosine Triphosphate

    KW - Potassium Channels

    KW - Cell Line

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    M3 - Article

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    SP - 121

    EP - 124

    JO - Proceedings of the Royal Society B

    JF - Proceedings of the Royal Society B

    SN - 0962-8452

    IS - 1319

    ER -