PMID- 18216164 OWN - NLM STAT- MEDLINE DCOM- 20080617 LR - 20200930 IS - 0363-6143 (Print) IS - 0363-6143 (Linking) VI - 294 IP - 4 DP - 2008 Apr TI - Evidence for KCNQ1 K+ channel expression in rat zymogen granule membranes and involvement in cholecystokinin-induced pancreatic acinar secretion. PG - C879-92 LID - 10.1152/ajpcell.00490.2007 [doi] AB - 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 approximately 10 microM). 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 microM 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 approximately 10 microM). Thus KCNQ1 may account for ZG K(+) conductance and contribute to pancreatic hormone-stimulated enzyme and fluid secretion. FAU - Lee, Wing-Kee AU - Lee WK AD - Department of Physiology & Pathophysiology, University of Witten/Herdecke, Witten, Germany. FAU - Torchalski, Blazej AU - Torchalski B FAU - Roussa, Eleni AU - Roussa E FAU - Thevenod, Frank AU - Thevenod F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080123 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Cholagogues and Choleretics) RN - 0 (Chromans) RN - 0 (Enzyme Precursors) RN - 0 (KCNQ1 Potassium Channel) RN - 0 (Kcnq1 protein, rat) RN - 0 (Sulfonamides) RN - 163163-23-3 (6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane) RN - 9011-97-6 (Cholecystokinin) RN - EC 3.2.1.- (Amylases) SB - IM MH - Amylases/metabolism MH - Animals MH - Cell Membrane/*metabolism MH - Cholagogues and Choleretics/pharmacology MH - Cholecystokinin/*pharmacology MH - Chromans/pharmacology MH - Enzyme Precursors MH - Gene Expression Regulation/physiology MH - Ion Channel Gating/drug effects MH - KCNQ1 Potassium Channel/antagonists & inhibitors/genetics/*metabolism MH - Male MH - Pancreas/enzymology/*metabolism MH - Rats MH - Rats, Wistar MH - Secretory Vesicles/enzymology/*metabolism MH - Sulfonamides/pharmacology EDAT- 2008/01/25 09:00 MHDA- 2008/06/18 09:00 CRDT- 2008/01/25 09:00 PHST- 2008/01/25 09:00 [pubmed] PHST- 2008/06/18 09:00 [medline] PHST- 2008/01/25 09:00 [entrez] AID - 00490.2007 [pii] AID - 10.1152/ajpcell.00490.2007 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2008 Apr;294(4):C879-92. doi: 10.1152/ajpcell.00490.2007. Epub 2008 Jan 23.