Ca Activated K+ Channel Kca3.1 as a Determinant of Gastric Acid Secretion.

The Ca²⁺ activated K⁺ channel K_ca3.1 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_ca3.1 activity for gastric acid secretion, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional K_ca3.1 (K_ca3.1^-/-) and from their wild type littermates (K_ca3.1^+/+). According to BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in K_ca3.1^-/- and K_ca3.1^+/+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_ca3.1^-/- than in K_ca3.1^+/+ mice. Accordingly, the luminal pH was significantly lower and the acid content significantly higher in K_ca3.1^-/- than in K_ca3.1^+/+ 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_ca3.1^+/+ than in K_ca3.1^-/- 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_ca3.1^-/- and K_ca3.1^+/+ mice. In K_ca3.1^+/+ mice the K_ca3.1 opener DCEBIO (100 μM) did not significantly alter basal ΔpH/min but significantly blunted ΔpH/min in the presence of carbachol. In conclusion, K_ca3.1 activity suppresses carbachol stimulated gastric acid secretion. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]