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Ca2+‐activated K+ channels mediate duodenal mucosal bicarbonate secretion
Author(s) -
Dong Hui,
Smith Anders,
Hovaida Marjan,
Chow Jimmy
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a843
Subject(s) - chemistry , in vivo , bicarbonate , perfusion , tetraethylammonium , endocrinology , medicine , pharmacology , biology , potassium , microbiology and biotechnology , organic chemistry
Duodenal mucosal bicarbonate secretion (DMBS) is currently accepted as a primary defense process against gastric acid, but the precise mechanism of DMBS has not been completely elucidated. The aim of the present study was to determine whether Ca 2+ ‐activated K + (K Ca ) channels are expressed in the duodenal mucosa and whether they are involved in Ca 2+ ‐mediated DMBS. DMBS was determined in vitro by pH‐stat and in vivo by using a CO 2 ‐sensitive electrode. Expression of K Ca in duodenal mucosae was analyzed by RT‐PCR. Clotrimazole (30 μM), a selective blocker for intermediate K Ca channels (IK Ca ), significantly inhibited carbachol (CCh)‐induced DMBS, but did not affect forskolin‐induced or heat‐stable enterotoxin of Escherichia coli (ST a )‐induced DMBS. TRAM‐34 (10 μM), another more potent and selective IK Ca channel blocker, also significantly inhibited CCh‐induced DMBS. However, tetraethylammonium, 4‐aminopyridine, and BaCl 2 , at concentrations known to block K + channels other than IK Ca , failed to inhibit CCh‐induced DMBS. A23187 (10 μM), a Ca 2+ ionophore, and 1‐EBIO (1 mM), a selective opener of K Ca channels, increased DMBS markedly more pronounced following serosal vs. mucosal addition. Again, both clotrimazole and TRAM‐34 significantly reduced A23187‐ or 1‐EBIO‐induced DMBS. Finally, duodenal luminal perfusion with 10 mM HCl increased DMBS in vivo , which was inhibited by 77% when mice were injected (i.p.) with 20 mg/kg clotromazole. Expression of mRNA for IK Ca channels was also detected in mouse duodenal mucosae by RT‐PCR analysis. Our results imply an important role for IK Ca in murine DMBS. An increase in [Ca 2+ ] i induced by cholinergic neurotransmitters may activate DMBS secondary to opening of basolateral IK Ca , thereby maintaining energetics favorable for duodenal HCO 3 − secretion.