title: Ca2+ activated K+ channel Kca3.1 as a determinant of gastric acid secretion.
abstract: The Ca(2+) activated K(+) channel K(ca)3.1 is expressed in a variety of tissues. In the gastric gland it is expressed in the basolateral cell membrane. To determine the functional significance of K(ca)3.1 activity for gastric acid secretion, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional K(ca)3.1 (K(ca)3.1(-/-)) and from their wild type littermates (K(ca)3.1(+/+)). According to BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in K(ca)3.1(-/-) and K(ca)3.1(+/+) mice. Na(ca)-independent pH recovery (ΔpH/min) following an ammonium pulse, a measure of H(ca)/K(ca) ATPase activity, was, however, significantly faster in K(ca)3.1(-/-) than in K(ca)3.1(+/+) mice. Accordingly, the luminal pH was significantly lower and the acid content significantly higher in K(ca)3.1(-/-) than in K(ca)3.1(+/+) mice. The abundance of mRNA encoding H(ca)/K(ca) ATPase and KCNQ1 was similar in both genotypes. Increase of extracellular K(ca) concentrations to 35 mM (replacing Na(ca)/NMDG) and treatment with histamine (100 μM) significantly increased ΔpH/min to a larger extent in K(ca)3.1(+/+) than in K(ca)3.1(-/-) mice and dissipated the differences between the genotypes. Carbachol (100 μM) increased ΔpH/min in both genotypes but did not abolish the difference between K(ca)3.1(-/-) and K(ca)3.1(+/+) mice. In K(ca)3.1(+/+) mice the K(ca)3.1 opener DCEBIO (100 μM) did not significantly alter basal ΔpH/min but significantly blunted ΔpH/min in the presence of carbachol. In conclusion, K(ca)3.1 activity suppresses carbachol stimulated gastric acid secretion.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstrasse 5, Tübingen, Germany.
authors.forename: Anand
authors.initials: A
authors.lastname: Rotte
authors.forename: Venkanna
authors.initials: V
authors.lastname: Pasham
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
authors.forename: Madhuri
authors.initials: M
authors.lastname: Bhandaru
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Melanie
authors.initials: M
authors.lastname: Eichenmüller
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D005452:Fluoresceins / Q000032:analysis; D005744:Gastric Acid / Q000201:enzymology* / Q000378:metabolism; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009853:Omeprazole / Q000494:pharmacology; D009924:Organ Culture Techniques; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011522:Protons; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D005452:Fluoresceins; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D051657:KCNQ1 Potassium Channel; C496925:Kcnn4 protein, mouse; D011522:Protons; D012333:RNA, Messenger; D000641:Ammonia; D006632:Histamine; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D002217:Carbachol; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D011188:Potassium; D002118:Calcium