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Expression of acid‐sensing ion channels in intestinal epithelial cells and their role in the regulation of duodenal mucosal bicarbonate secretion
Author(s) -
Dong X.,
Ko K. H.,
Chow J.,
Tuo B.,
Barrett K. E.,
Dong H.
Publication year - 2011
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2010.02207.x
Subject(s) - amiloride , acidosis , channel blocker , extracellular , acid sensing ion channel , secretion , endocrinology , medicine , purinergic receptor , ion transporter , ionomycin , biology , chemistry , microbiology and biotechnology , calcium , ion channel , receptor , biochemistry , stimulation , sodium , organic chemistry , membrane
Aims: As little is currently known about acid‐sensing ion channels (ASICs) in intestinal epithelial cells, the aims of the present study were to investigate the expression and function of ASICs in intestinal epithelial cells, particularly their physiological role in the acid‐stimulated duodenal mucosal bicarbonate secretion (DMBS). Methods: RT‐PCR and digital Ca 2+ imaging were used to determine the expression and function of ASICs in HT29 cells and SCBN cells, intestinal epithelial crypt cell lines. The acid‐stimulated DMBS was measured in C57 black mice in vivo to study the role of ASICs in this physiological process. Results: ASIC1a mRNA expression was detected in the duodenal mucosa stripped from mice and epithelial cell lines, in which cytoplasmic free Ca 2+ ([Ca 2+ ] cyt ) in response to extracellular acidosis was also increased. In Ca 2+ ‐containing solutions, acidosis (pH 6.0‐5.0) raised [Ca 2+ ] cyt in both HT29 cells and SCBN cells in a similar pH‐dependent manner. Acidosis‐induced increase in [Ca 2+ ] cyt was markedly inhibited by amiloride (an ASICs blocker), SK&F96365 (a blocker for non‐selective cation channels), or in Ca 2+ ‐free solutions; but was abolished by amiloride in Ca 2+ ‐free solutions. However, acidosis‐induced increase in [Ca 2+ ] cyt was slightly affected by U73122 (a PLC inhibitor), or nifedipine (a voltage‐gated Ca 2+ channel blocker). After acidosis raised [Ca 2+ ] cyt , stimulation of purinergic receptors with ATP further increased [Ca 2+ ] cyt , but acidosis‐induced increase in [Ca 2+ ] cyt was not altered by suramin. Moreover, acid‐stimulated murine DMBS was significantly attenuated by amiloride. Conclusion: Therefore, ASICs are functionally expressed in intestinal epithelial cells, and may play a role in acid‐stimulated DMBS through a Ca 2+ signalling pathway.