HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/G1015    most recent 00468.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Gawenis, L. R. Articles by Clarke, L. L. Search for Related Content PubMed PubMed Citation Articles by Gawenis, L. R. Articles by Clarke, L. L.

MUCOSAL BIOLOGY

Lateral intercellular space volume as a determinant of CFTR-mediated anion secretion across small intestinal mucosa

Dalton Cardiovascular Research Center and the Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri 65211

Submitted 5 November 2003 ; accepted in final form 29 January 2004

Studies of full-thickness, small intestinal preparations have shown that maximal anion secretion [indexed by short-circuit current (I_sc)] during intracellular cAMP (cAMP_i) stimulation is transient and followed by a decline toward baseline. Declining I_sc is preceded by decreases in transepithelial conductance (G_t), which in the small intestine reflects the lateral intercellular space (LIS) volume of the paracellular pathway. We hypothesized that decreases in LIS volume limit the magnitude and duration of cAMP_i-stimulated anion secretion. Experimental manipulations to increase the patency of the LIS (assessed by G_t and electron microscopy) were investigated for an effect on the magnitude of cAMP_i-stimulated anion secretion (assessed by the I_sc and isotopic fluxes) across murine small intestine. In control studies, changes of G_t after cAMP_i stimulation were associated with a morphological "collapse" of the LIS, which did not occur in intestine of CFTR-null mice. Removal of the outer intestinal musculature, exposure to a serosal hypertonic solution, or increased serosal hydrostatic pressure minimized reductions in G_t and increased the cAMP_i-stimulated I_sc response. Increased I_sc primarily resulted from increased Cl^– secretion that was largely bumetanide sensitive. However, bumetanide-insensitive I_sc was also increased, and similar increases occurred in the Na⁺-K⁺-2Cl^– cotransporter (NKCC1)-null intestine, indicating that activities of non-NKCC1 anion uptake proteins are also affected by LIS volume. Thus LIS patency is an important determinant of the magnitude and duration of CFTR-mediated anion secretion in murine small intestine. Decreases in LIS volume may limit the pool of available anions to basolateral transporters involved in transepithelial secretion.

bicarbonate; chloride; tight junction; Na⁺-K⁺-2Cl^– cotransporter; cystic fibrosis; mouse

This article has been cited by other articles:

				L. L. Clarke A guide to Ussing chamber studies of mouse intestine Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1151 - G1166. [Abstract] [Full Text] [PDF]

				A. T. Blikslager, A. J. Moeser, J. L. Gookin, S. L. Jones, and J. Odle Restoration of Barrier Function in Injured Intestinal Mucosa Physiol Rev, April 1, 2007; 87(2): 545 - 564. [Abstract] [Full Text] [PDF]

				K. J Treharne, R. M Crawford, and A Mehta CFTR, chloride concentration and cell volume: could mammalian protein histidine phosphorylation play a latent role? Exp Physiol, January 1, 2006; 91(1): 131 - 139. [Abstract] [Full Text] [PDF]

				L. R. Gawenis, H. Hut, A. G. M. Bot, G. E. Shull, H. R. de Jonge, X. Stien, M. L. Miller, and L. L. Clarke Electroneutral sodium absorption and electrogenic anion secretion across murine small intestine are regulated in parallel Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1140 - G1149. [Abstract] [Full Text] [PDF]