Functional Role of Basolateral ClC-2 Channels in the Regulation of Duodenal Anion Secretion in Mice

  • Chao Du
  • Jingjing Liu
  • Hanxing Wan
  • Hui DongEmail author
  • Xiaoyan ZhaoEmail author
Original Article



Although ClC-2 channels are important in colonic Cl secretion, it is unclear about their roles in small intestinal anion secretion. Therefore, we sought to examine whether ClC-2 channels play important roles in anion secretion, particularly duodenal bicarbonate secretion (DBS).


Duodenal mucosae from mice were stripped of seromuscular layers and mounted in Ussing chambers. Both duodenal short-circuit current (Isc) and HCO3 secretion in vitro were simultaneously recorded. DBS in vivo was measured by a CO2-sensitive electrode.


Lubiprostone, a selective ClC-2 activator, concentration-dependently increased both duodenal Isc and DBS only when applied basolaterally, but not when applied apically. Removal of extracellular Cl abolished lubiprostone-induced duodenal Isc, but did not alter HCO3 secretion even in the presence of DIDS, a Cl/HCO3 exchanger inhibitor. However, further addition of glibenclamide, a CFTR channel blocker, abolished lubiprostone-evoked HCO3 secretion. Moreover, lubiprostone-induced HCO3 secretion was impaired in CFTR−/− mice compared to wild-type littermates. Luminal perfusion of duodenal lumen with lubiprostone did not alter basal DBS in vivo, but lubiprostone (i.p.) was able to induce DBS, which was also significantly inhibited by Cd2+, a ClC-2 channel blocker. [Ca2+]cyt level, Ca2+-activated K+ channel- and cAMP-mediated duodenal Isc, and HCO3 secretion were unchanged by lubiprostone.


We have provided the first evidence for the novel functional role of basolateral ClC-2 channels in the regulation of duodenal anion secretion.


ClC-2 Duodenal Bicarbonate secretion CFTR 



Cystic fibrosis transmembrane conductance regulator


Duodenal bicarbonate secretion


Anion exchangers


Na+/HCO3 cotransporters


Transepithelial resistance



These studies were supported by research grants from the National Key Research and Development Program of China (No. 2016YFC1302200 to HD) and the National Natural Science Foundation of China (Nos. 81570477 and 81873544 to HD).

Author's contribution

HD designed and supervised the project, wrote and finalized the manuscript. CD and JL conducted most experiments and data analysis. HXW conducted some experiments. XZ finalized the manuscript. All authors reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology, Xinqiao HospitalArmy Medical UniversityChongqingChina
  2. 2.Department of Medicine, School of MedicineUniversity of CaliforniaSan DiegoUSA

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