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.