Brought to you by Portland Press Ltd.
Published on behalf of the International Federation for Cell Biology
Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2010) 34, 99–108 (Printed in Great Britain)
Trimethyltin chloride induced chloride secretion across rat distal colon
Haijie Yu*, Siliang Chen*, Zihuan Yang*, Ao Pan*, Geng Zhang*, Jiajie Shan*, Xiaojiang Tang† and Wenliang Zhou*1
*The School of Life Science, Sun Yat-sen University, Guangzhou 510275, China, and †Department of Toxicology, Guangdong Provincial Center for Occupational Disease Prevention and Treatment, Guangzhou, China

TMT (trimethyltin chloride), an organotin, is ubiquitous in the environment. The consumption of contaminated food may cause exposure of the human diet to this toxic compound. The present study was to investigate the effects of TMT on the regulation of ion transport across the rat distal colon. The rat colonic mucosa was mounted in Ussing chambers. The effects of TMT were assessed using the Isc (short-circuit current). Both apical and basolateral TMT induced, dose-dependently, an increase in Isc, which was due to a stimulation of Cl secretion as measured using ion substitution experiments and pharmacological manoeuvres. The secretion was also inhibited by several K+ channel blockers administrated at the basolateral side. When the apical side was permeabilized by nystatin, the TMT-induced K+ conductance was effectively blocked by tetrapentylammonium, a Ca2+-sensitive K+ channel blocker. The response of TMT was sensitive to the basolateral Ca2+ and the intracellular Ca2+ store, which could be disclosed by applying the inhibitors of ryanodine receptors and inositol 1,4,5-trisphosphate receptors. In conclusion, TMT led to Cl secretion, which was essentially regulated by basolateral Ca2+-sensitive K+ channels. These results suggest the importance of K+ channels in the toxicity hazard of TMT.

Key words: Cl secretion, cystic fibrosis transmembrane conductance regulator (CFTR), K+ channel, rat distal colon, short circuit current, trimethyltin chloride

Abbreviations: 2-APB, 2-aminoethoxydiphenylborate, CA, carbonic anhydrase, (Ca2+)i, intracellular Ca2+, CF, cystic fibrosis, CFTR, CF transmembrane conductance regulator, COX, cyclo-oxygenase, CRAC, Ca2+ release-activated channel, DIDS, 4,4′-diisothiocyanato-stilbene-2, 2′-disulfonic acid, DPC, diphenylamine-2-carboxylate, ENaC, epithelial Na+ channel, IP3, inositol triphosphate, Isc, short-circuit current, KH, Krebs–Henseleit, NKCC, Na+-K+-2Cl symport, PD, potential electrical difference, Rt, resistance, RyR, ryanodine receptor, TEA, tetraethylammonium, TMT, trimethyltin chloride, TPeA, tetrapentylammonium

1To whom correspondence should be addressed (email

Received 18 June 2009/11 August 2009; accepted 16 September 2009

Published as Cell Biology International Immediate Publication 16 September 2009, doi:10.1042/CBI20090022

© 2010 The Author(s) Journal compilation. © 2010 Portland Press Ltd

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)