Nucleotide Regulation of a calcium-activated cation channel in the rat insulinoma cell line, CRI-G1

V. Reale, C. N. Hales, M. L. Ashford

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    The nucleotide regulation of a calcium-activated nonselective cation (Ca-NS+) channel has been investigated in the rat insulinoma cell line CRI-G1. The activity of the channel is reduced by both AMP and ADP (1-100 microM) in a concentration-dependent manner, with AMP being more potent than ADP. At lower concentrations (0.1-5 microM), both ADP and AMP activate the channel in some patches. Examination of the nucleotide specificity of channel inhibition indicates a high selectivity for AMP over the other nucleotides tested with a rank order of potency of AMP > UMP > CMP > or = GMP. Cyclic nucleotides also modulate channel activity in a complex, concentration-dependent way. Cyclic AMP exhibits a dual effect, predominantly increasing channel activity at low concentrations (0.1-10 microM) and reducing it at higher concentrations (100 microM and 1 mM). Specificity studies indicate that the cyclic nucleotide site mediating inhibition of channel activity exhibits a strong preference for cyclic AMP over cyclic GMP, with cyclic UMP being almost equipotent with cyclic AMP. Cyclic IMP and cyclic CMP are not active at this site. The cyclic nucleotide site mediating activation of the channel shows much less nucleotide specificity than the inhibitory site, with cyclic AMP, cyclic GMP and cyclic IMP being almost equally active.
    Original languageEnglish
    Pages (from-to)101-112
    Number of pages12
    JournalJournal of Membrane Biology
    Volume141
    Issue number2
    DOIs
    Publication statusPublished - 1994

    Keywords

    • Adenosine Monophosphate
    • Animals
    • Calcium
    • Ribonucleotides
    • Pancreatic Neoplasms
    • Insulinoma
    • Ion Channels
    • Uridine Monophosphate
    • Structure-Activity Relationship
    • Rats
    • Adenosine Diphosphate
    • Tumor Cells, Cultured
    • Kinetics
    • Membrane Potentials
    • Cell Line
    • Cytidine Monophosphate
    • Guanosine Monophosphate

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