Expression of acid-sensing ion channels in intestinal epithelial cells and their role in the regulation of duodenal mucosal bicarbonate secretion.

Abstract

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 Ca²(+) 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 Ca²(+) ([Ca²(+) ](cyt)) in response to extracellular acidosis was also increased. In Ca²(+) -containing solutions, acidosis (pH 6.0-5.0) raised [Ca²(+) ](cyt) in both HT29 cells and SCBN cells in a similar pH-dependent manner. Acidosis-induced increase in [Ca²(+) ](cyt) was markedly inhibited by amiloride (an ASICs blocker), SK&F96365 (a blocker for non-selective cation channels), or in Ca²(+) -free solutions; but was abolished by amiloride in Ca²(+) -free solutions. However, acidosis-induced increase in [Ca²(+) ](cyt) was slightly affected by U73122 (a PLC inhibitor), or nifedipine (a voltage-gated Ca²(+) channel blocker). After acidosis raised [Ca²(+) ](cyt) , stimulation of purinergic receptors with ATP further increased [Ca²(+) ](cyt) , but acidosis-induced increase in [Ca²(+) ](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 Ca²(+) signalling pathway.

• Authors: X Dong, K H Ko, J Chow, B Tuo, K E Barrett, H Dong
• Journal: Acta physiologica (Oxford, England) (Acta Physiol (Oxf)) Vol. 201 Issue 1 Pg. 97-107 (Jan 2011) ISSN: 1748-1716 [Electronic] England
• PMID: 20969730 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Acta Physiologica © 2010 Scandinavian Physiological Society.

Chemical References

• ASIC1 protein, human
• ASIC1 protein, mouse
• Acid Sensing Ion Channels
• Bicarbonates
• Nerve Tissue Proteins
• Sodium Channel Blockers
• Sodium Channels
• Suramin
• Amiloride
• Calcium

Topics

• Acid Sensing Ion Channels
• Amiloride (metabolism)
• Animals
• Bicarbonates (metabolism)
• Calcium (metabolism)
• Cell Line
• Duodenum (metabolism)
• Epithelial Cells (cytology, metabolism)
• Humans
• Hydrogen-Ion Concentration
• Intestinal Mucosa (cytology)
• Mice
• Mice, Inbred C57BL
• Nerve Tissue Proteins (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction (physiology)
• Sodium Channel Blockers (metabolism)
• Sodium Channels (genetics, metabolism)
• Suramin (metabolism)