Gap junction communication modulates [Ca²⁺]_i oscillations and enzyme secretion in pancreatic acini

Global (all cells in an acinus) and focal (1-2 out of 10-15 cells) stimulation of pancreatic acini with bombesin or t-butyloxycarbonyl-Tyr(SO₃)-Nle-Gly-Tyr-Asp-2-phenylethyl ester (CCKJ) together with modulation of gap junction (GJ) permeability by octanol and NO₂^- was used to study the role of GJ permeability in controlling [Ca²⁺]_i oscillations and enzyme secretion. GJ permeability was quantitated by measuring fluorescence recovery after photobleaching. Octanol at 0.5 mM markedly reduced, whereas 15 mM NO₂^- increased GJ permeability. Focal application of bombesin caused synchronized oscillations in the entire acinus, whereas global stimulation resulted in asynchronous oscillations. Increasing GJ permeability with NO₂^- had no effect on bombesin-evoked [Ca²⁺]_i- oscillations. Octanol inhibited ongoing oscillations evoked by focal or global bombesin stimulation. However, when GJ were blocked prior to stimulation, subsequent global stimulation with bombesin induced long-lasting oscillations in all cells. Re-establishing GJ communication for as little as 37.5 s conferred GJ dependence on the order and time of [Ca²⁺]_i spiking evoked by global bombesin stimulation. Focal and global stimulation with CCKJ gave different patterns of [Ca²⁺]_i- oscillations. However, in contrast to bombesin, inhibition of GJ with octanol had no effect on oscillations induced by global CCKJ stimulation. Increasing GJ permeability with NO₂^- synchronized CCKJ-stimulated oscillations by equalizing the amplitude and increasing the frequency in all cells within an acinus. These observations suggest that amplitude and frequency of [Ca²⁺]_i oscillations can be regulated independently of each other, and that GJ permeable molecules modulate the frequency of [Ca²⁺]_i-oscillation in an agonist-specific manner. Regardless of the agonist, increasing the frequency of oscillations by modulation of GJ permeability correlated with an increased enzyme secretion.