Rotte Anand, Pasham Venkanna, Mack Andreas F, Bhandaru Madhuri, Qadri Syed M, Eichenmüller Melanie, Ruth Peter, Lang Florian
Department of Physiology, University of Tübingen, Gmelinstrasse 5, Tübingen, Germany.
Cell Physiol Biochem. 2011;27(5):597-604. doi: 10.1159/000329981. Epub 2011 Jun 15.
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.
钙激活钾通道K(ca)3.1在多种组织中表达。在胃腺中，它表达于基底外侧细胞膜。为了确定K(ca)3.1活性对胃酸分泌的功能意义，我们在缺乏功能性K(ca)3.1的基因靶向小鼠（K(ca)3.1(-/-)）及其野生型同窝小鼠（K(ca)3.1(+/+)）的分离胃腺中测定了胃酸分泌。根据BCECF荧光，分离胃腺中的细胞溶质pH在K(ca)3.1(-/-)和K(ca)3.1(+/+)小鼠中相似。然而，铵脉冲后不依赖钠的pH恢复（ΔpH/分钟），即H(ca)/K(ca)ATP酶活性的一种度量，在K(ca)3.1(-/-)小鼠中比在K(ca)3.1(+/+)小鼠中显著更快。因此，K(ca)3.1(-/-)小鼠的管腔pH显著更低，酸含量显著更高。两种基因型中编码H(ca)/K(ca)ATP酶和KCNQ1的mRNA丰度相似。将细胞外钾浓度增加到35 mM（替代钠/ NMDG）并用组胺（100 μM）处理，在K(ca)3.1(+/+)小鼠中比在K(ca)3.1(-/-)小鼠中更显著地增加ΔpH/分钟，并消除了基因型之间的差异。卡巴胆碱（100 μM）在两种基因型中均增加ΔpH/分钟，但未消除K(ca)3.1(-/-)和K(ca)3.1(+/+)小鼠之间的差异。在K(ca)3.1(+/+)小鼠中，K(ca)3.1开放剂DCEBIO（100 μM）在基础状态下未显著改变ΔpH/分钟，但在存在卡巴胆碱时显著减弱了ΔpH/分钟。总之，K(ca)3.1活性抑制卡巴胆碱刺激的胃酸分泌。
