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• W2164328772 abstract "Secretion of enzymes and fluid induced by Ca 2+ in pancreatic acini is not completely understood and may involve activation of ion conductive pathways in zymogen granule (ZG) membranes. We hypothesized that a chromanol 293B-sensitive K + conductance carried by a KCNQ1 protein is expressed in ZG membranes (ZGM). In suspensions of rat pancreatic ZG, ion flux was determined by ionophore-induced osmotic lysis of ZG suspended in isotonic salts. The KCNQ1 blocker 293B selectively blocked K + permeability (IC 50 of ∼10 μM). After incorporation of ZGM into planar bilayer membranes, cation channels were detected in 645/150 mM potassium gluconate cis/trans solutions. Channels had linear current-voltage relationships, a reversal potential ( E rev ) of −20.9 ± 0.9 mV, and a single-channel K + conductance ( g K ) of 265.8 ± 44.0 pS ( n = 39). Replacement of cis 500 mM K + by 500 mM Na + shifted E rev to −2.4 ± 3.6 mV ( n = 3), indicating K + selectivity. Single-channel analysis identified several K + channel groups with distinct channel behaviors. K + channels with a g K of 651.8 ± 88.0 pS, E rev of −22.9 ± 2.2 mV, and open probability ( P open ) of 0.43 ± 0.06 at 0 mV ( n = 6) and channels with a g K of 155.0 ± 11.4 pS, E rev of −18.3 ± 1.8 mV, and P open of 0.80 ± 0.03 at 0 mV ( n = 3) were inhibited by 100 μM 293B or by the more selective inhibitor HMR-1556 but not by the maxi-Ca 2+ -activated K + channel (BK channel) inhibitor charybdotoxin (5 nM). KCNQ1 protein was demonstrated by immunoperoxidase labeling of pancreatic tissue, immunogold labeling of ZG, and immunoblotting of ZGM. 293B also inhibited cholecystokinin-induced amylase secretion of permeabilized acini (IC 50 of ∼10 μM). Thus KCNQ1 may account for ZG K + conductance and contribute to pancreatic hormone-stimulated enzyme and fluid secretion." @default.
• W2164328772 created "2016-06-24" @default.
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• W2164328772 date "2008-04-01" @default.
• W2164328772 modified "2023-09-23" @default.
• W2164328772 title "Evidence for KCNQ1 K⁺channel expression in rat zymogen granule membranes and involvement in cholecystokinin-induced pancreatic acinar secretion" @default.
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• W2164328772 doi "https://doi.org/10.1152/ajpcell.00490.2007" @default.
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