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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/C879    most recent 00490.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Lee, W.-K. Articles by Thévenod, F. Search for Related Content PubMed PubMed Citation Articles by Lee, W.-K. Articles by Thévenod, F.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Evidence for KCNQ1 K⁺ channel expression in rat zymogen granule membranes and involvement in cholecystokinin-induced pancreatic acinar secretion

¹Department of Physiology and Pathophysiology, University of Witten/Herdecke, Witten, Germany; and ²Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, Freiburg, Germany

Submitted 17 October 2007 ; accepted in final form 18 January 2008

Secretion of enzymes and fluid induced by Ca²⁺ 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 (IC₅₀ 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-Ca²⁺-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 (IC₅₀ of 10 µM). Thus KCNQ1 may account for ZG K⁺ conductance and contribute to pancreatic hormone-stimulated enzyme and fluid secretion.

exocytosis; acinar cell; secretory granule; planar bilayer