Abstract
GLUCOSE-STIMULATED insulin secretion is associated with the appearance of electrical activity in the pancreatic β-cell. At intermediate glucose concentrations, β-cell electrical activity follows a characteristic pattern of slow oscillations in membrane potential on which bursts of action potentials are superimposed1. The electro-physiological background of the bursting pattern remains unestablished. Activation of Ca2+-activated large-conductance K+ channels (KCa channel2) has been implicated in this process3 but seems unlikely in view of recent evidence demonstrating that the β-cell electrical activity is unaffected by the specific KCa channel blocker charybdotoxin4. Another hypothesis postulates that the bursting arises as a consequence of two components of Ca2+-current inactivation5. Here we show that activation of a novel Ca2+-dependent K+ current in glucose-stimulated β-cells produces a transient membrane repolarization. This interrupts action potential firing so that action potentials appear in bursts. Spontaneous activity of this current was seen only rarely but could be induced by addition of compounds functionally related to hormones and neurotransmitters present in the intact pancreatic islet. K+ currents of the same type could be evoked by intracellular application of GTP, the effect of which was mediated by mobilization of Ca2+ from inositol 1,4,5-trisphosphate (InsP3)-sensitive intracellular Ca2+ stores. These observations suggest that oscillatory glucose-stimulated electrical activity, which is correlated with pulsatile release of insulin6, results from the interaction between the β-cell and intraislet hormones and neurotransmitters. Our data also provide evidence for a close interplay between ion channels in theplasma membrane and InsP3-induced mobilization of intracellular Ca2+ in an excitable cell.
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Ämmälä, C., Larsson, O., Berggren, PO. et al. Inositol trisphosphate-dependent periodic activation of a Ca2+-activated K+ conductance in glucose-stimulated pancreatic β-cells. Nature 353, 849–852 (1991). https://doi.org/10.1038/353849a0
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DOI: https://doi.org/10.1038/353849a0
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