Ca 2+ activated K + channel K ca 3.1 as a determinant of gastric acid secretion

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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. © 2011 S. Karger AG, Basel.

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Rotte, A., Pasham, V., MacK, A. F., Bhandaru, M., Qadri, S. M., Eichenmüller, M., … Lang, F. (2011). Ca 2+ activated K + channel K ca 3.1 as a determinant of gastric acid secretion. Cellular Physiology and Biochemistry, 27(5), 597–604. https://doi.org/10.1159/000329981

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