This preclinical study demonstrates that the run-down of ATP-sensitive K+ channel activity in insulin-secreting cells is dependent on intracellular Mg2+ concentration.
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ATP-sensitive K(+)-channel currents were recorded from isolated membrane patches and voltage-clamped CRI-G1 insulin-secreting cells. Internal Mg2+ ions inhibited ATP-K+ channels by a voltage-dependent block of the channel current and decrease of open-state probability. The run-down of ATP-K+ channel activity was also shown to be [Mg2+]i dependent, being almost abolished in Mg2(+)-free conditions. Substitution of Mn2+ for Mg2+ did not prevent run-down, nor did the presence of phosphate-donating nucleotides, a protease or phosphatase inhibitor or replacement of Cl- by gluconate.
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Mg2+-dependent KATP run-down in beta cells is hypothesis-generating; requires validation in intact systems before physiological relevance.
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Kozlowski et al. (1990) studied this question.
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