Characterization of a nicotinamide-adenine dinucleotide-dependent cation channel in the CRI-G1 rat insulinoma cell line

P. S. Herson, K. A. Dulock, M. L. J. Ashford

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    31 Citations (Scopus)


    1. Cell-free excised membrane patches were used to examine the properties of a novel nicotinamide-adenine dinucleotide (beta-NAD+)-activated ion channel in the rat insulin-secreting cell line, CRI-G1. 2. In inside-out recordings, beta-NAD+ (0.05-1.0 mM) induced the appearance of a channel characterized by extremely slow kinetics, with mean open times in the range of seconds. The estimated EC50 for activation was 114 microM. Channel activity declined with time (run-down) following activation by beta-NAD+ in excised patches and this was not prevented by intracellular application of trypsin. 3. The single channel current-voltage relationship was linear with a conductance of 74 pS in symmetrical NaCl. The channel appears equally permeable to Na+, K+ and Cs+, exhibits an appreciable permeability to Ca2+, Mg2+ and Ba2+, but excludes anions. 4. The channel displays an unusual voltage sensitivity, with an abrupt increase in open-state probability at depolarized voltages. 5. Channel opening, in the presence of beta-NAD+, required both Ca2+ and Mg2+ to be present at the internal side of the membrane. Activation by Ca2+ required a concentration of at least 10 microM and was maximal at 0.1 mM. Ba2+ did not substitute for Ca2+ in inducing channel activity nor did it inhibit activation by Ca2+. Increasing the concentration of intracellular Mg2+ stabilized the open state of NAD(+)-activated channels. 6. The non-selective cation channel reported here differs in its gating and modulatory characteristics from non-selective cation channels described in other tissues. This channel may play a role in the pathophysiological responses of beta-cells to oxidative stress.
    Original languageEnglish
    Pages (from-to)65-76
    Number of pages12
    JournalJournal of Physiology
    Issue number( Pt 1)
    Publication statusPublished - 1997


    • Animals
    • Ion Channel Gating
    • Calcium
    • Insulinoma
    • Ion Channels
    • Islets of Langerhans
    • Electrophysiology
    • Rats
    • Patch-Clamp Techniques
    • Tumor Cells, Cultured
    • NAD
    • Barium
    • Kinetics
    • Oxidative Stress
    • Membrane Potentials
    • Magnesium


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