Activation of glycine and glutamate receptors increases intracellular calcium in cells derived from the endocrine pancreas.

Weaver CD, Partridge JG, Yao TL, Moates JM, Magnuson MA, Verdoorn TA
Mol Pharmacol. 1998 54 (4): 639-46

PMID: 9765506

We studied calcium signaling in a newly described pancreatic cell line, GK-P3, that expresses functional amino acid neurotransmitter receptors. GK-P3 cells express the first strychnine-sensitive glycine receptors reported in a permanent cell line. In addition, GK-P3 cells express alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. Both types of amino acid receptors showed electrophysiological and pharmacological behavior similar to their neuronal counterparts. The glycine receptors were permeable to Cl- and blocked by the selective antagonist strychnine. AMPA receptors showed limited permeability to Ca2+, were blocked by 6-cyano-2, 3-dihydroxy-7-nitroquinoxaline, and were potentiated by cyclothiazide. Interestingly, activation of either receptor type increased intracellular Ca2+ measured by digital imaging of Fura-2 fluorescence. These Ca2+ signals were completely blocked by 30 microM La3+, suggesting that the Ca2+ entered the cells largely through voltage-dependent Ca2+ channels. Alterations in the extracellular concentrations of Cl- and/or HCO3- had only marginal effects on glycine-evoked Ca2+ signals. However, increases in intracellular Ca2+ mediated by AMPA receptors were absent when the extracellular Na+ was replaced with an impermeant cation, N-methyl-D-glucamine. We conclude that activation of ligand-gated cation or anion channels depolarize GK-P3 cells sufficiently to activate their voltage-gated Ca2+ channels leading to increases in intracellular Ca2+ concentration. Thus, glycine and glutamate receptors may regulate Ca2+-dependent secretory mechanisms in islet cells by altering the membrane potential of these cells. Our data in GK-P3 cells support the growing weight of evidence for a role of amino acid neurotransmitters in pancreatic islets and introduce strychnine-sensitive glycine receptors as a novel target of amino acid neurotransmitter regulation in islets.

MeSH Terms (16)

Animals Calcium Calcium Signaling Ion Channel Gating Islets of Langerhans Membrane Potentials Mice Mice, Transgenic Neurons Rats Receptors, AMPA Receptors, GABA Receptors, Glutamate Receptors, Glycine Sensitivity and Specificity Strychnine

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