Amendments to the theory underlying Ussing chamber data of chloride ion secretion after bacterial enterotoxin exposure

Lucas, M.L. (2005) Amendments to the theory underlying Ussing chamber data of chloride ion secretion after bacterial enterotoxin exposure. Journal of Theoretical Biology, 234(1), pp. 21-37. (doi: 10.1016/j.jtbi.2004.11.005)

Abstract

Bacterial enterotoxins may cause life-threatening diarrhoeal fluid loss in part because they stimulate enterocytes to secrete fluid into the small intestine as well as preventing normal fluid uptake. Abnormal chloride ion secretion is believed to provide the osmotic driving force for the inappropriate fluid movement. Evidence for enhanced chloride secretion consists of isotopic flux measurements in Ussing chambers, the standard apparatus for permeation studies. Flux from the lumen of the intestine is assumed to be determined solely by absorptive processes and flux towards the lumen solely by secretory processes. Bacterial enterotoxin increased flux towards the lumen is taken as an evidence of enhanced secretion. Examination of the flux equation solutions shows that the existing theoretical treatment of the Ussing chamber consists of the super-imposition of two contradictory unidirectional models. In contrast, the present analysis shows that a measured ‘unidirectional’ flux contains information both about absorptive and secretory processes, regardless of which flux is measured. Reciprocity is predicted for the fluxes, as decreases in the absorptive processes will cause increases in apparent secretory flux. Data from the literature show that mucosal-to-serosal chloride ion flux in rabbit ileum after exposure to secretagogues correlates inversely and highly significantly with increases in serosal-to-mucosal chloride ion flux. As a category of evidence, flux data do not provide conclusive evidence of enhanced chloride secretion after exposure to enterotoxins, since an apparently enhanced serosal-to-mucosal flux would also be noted after inhibition of the mucosal-to-serosal flux. As interruption of absorptive processes can be misinterpreted as enhanced secretion in the Ussing chamber, this is a serious deficiency in the evidence for direct enterotoxin enhancement of the intestinal chloride ion channel as a basis for diarrhoeal disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lucas, Dr Michael
• Authors: Lucas, M.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Journal of Theoretical Biology
• ISSN: 0022-5193
• ISSN (Online): 1095-8541
• Published Online: 28 December 2004