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• W2912873485 startingPage "E646" @default.
• W2912873485 abstract "Pancreatic α-cells exhibit oscillations in cytosolic Ca 2+ (Ca 2+ c ), which control pulsatile glucagon (GCG) secretion. However, the mechanisms that modulate α-cell Ca 2+ c oscillations have not been elucidated. As β-cell Ca 2+ c oscillations are regulated in part by Ca 2+ -activated K + (K slow ) currents, this work investigated the role of K slow in α-cell Ca 2+ handling and GCG secretion. α-Cells displayed K slow currents that were dependent on Ca 2+ influx through L- and P/Q-type voltage-dependent Ca 2+ channels (VDCCs) as well as Ca 2+ released from endoplasmic reticulum stores. α-Cell K slow was decreased by small-conductance Ca 2+ -activated K + (SK) channel inhibitors apamin and UCL 1684, large-conductance Ca 2+ -activated K + (BK) channel inhibitor iberiotoxin (IbTx), and intermediate-conductance Ca 2+ -activated K + (IK) channel inhibitor TRAM 34. Moreover, partial inhibition of α-cell K slow with apamin depolarized membrane potential ( V m ) (3.8 ± 0.7 mV) and reduced action potential (AP) amplitude (10.4 ± 1.9 mV). Although apamin transiently increased Ca 2+ influx into α-cells at low glucose (42.9 ± 10.6%), sustained SK (38.5 ± 10.4%) or BK channel inhibition (31.0 ± 11.7%) decreased α-cell Ca 2+ influx. Total α-cell Ca 2+ c was similarly reduced (28.3 ± 11.1%) following prolonged treatment with high glucose, but it was not decreased further by SK or BK channel inhibition. Consistent with reduced α-cell Ca 2+ c following prolonged K slow inhibition, apamin decreased GCG secretion from mouse (20.4 ± 4.2%) and human (27.7 ± 13.1%) islets at low glucose. These data demonstrate that K slow activation provides a hyperpolarizing influence on α-cell V m that sustains Ca 2+ entry during hypoglycemic conditions, presumably by preventing voltage-dependent inactivation of P/Q-type VDCCs. Thus, when α-cell Ca 2+ c is elevated during secretagogue stimulation, K slow activation helps to preserve GCG secretion." @default.
• W2912873485 created "2019-02-21" @default.
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• W2912873485 date "2019-04-01" @default.
• W2912873485 modified "2023-10-16" @default.
• W2912873485 title "Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion" @default.
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• W2912873485 doi "https://doi.org/10.1152/ajpendo.00342.2018" @default.
• W2912873485 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6482666" @default.
• W2912873485 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30694690" @default.
• W2912873485 hasPublicationYear "2019" @default.
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