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: 290/6/G1219    most recent 00032.2005v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Wouters, M. Articles by Vanderwinden, J.-M. Search for Related Content PubMed PubMed Citation Articles by Wouters, M. Articles by Vanderwinden, J.-M.

NEUROREGULATION AND MOTILITY

Subtractive hybridization unravels a role for the ion cotransporter NKCC1 in the murine intestinal pacemaker

¹Laboratoire de Neurophysiology, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium; ²Department of Gastrointestinal Pharmacology, Johnson and Johnson, Pharmaceutical Research and Development, a Division of Janssen Pharmaceutica, Beerse, Belgium; ³Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium; ⁴Laboratory of Electrobiology, University of Antwerp, Antwerp, Belgium; and ⁵Department of Anesthesiology, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee

Submitted 26 January 2005 ; accepted in final form 12 August 2005

In the small intestine, interstitial cells of Cajal (ICC) surrounding the myenteric plexus generate the pacemaking slow waves that are essential for an efficient intestinal transit. The underlying molecular mechanisms of the slow wave are poorly known. Our aim was to identify ICC-specific genes and their function in the mouse jejunum. Suppression subtractive hybridization using two independent ICC-deficient mouse models identified 56 genes putatively downregulated in the muscularis propria compared with wild-type littermates. Differential expression was confirmed by real-time quantitative PCR for the tyrosine kinase receptor KIT, the established marker for ICC, and for the Na⁺-K⁺-2Cl^– cotransporter (NKCC1). Immunoreactivity for NKCC1 was detected in myenteric ICC but not in the ICC population located at the deep muscular plexus. NKCC1 was also expressed in enteric neurons and mucosal crypts. Bumetanide, an NKCC1 inhibitor, reversibly affected the shape, amplitude, and frequency of the slow waves. Similar alterations were observed in NKCC1 knockout mice. These data support the hypothesis that NKCC1 expressed in myenteric ICC is involved in the mechanism of slow waves in the murine jejunum.

interstitial cells of Cajal; bumetanide; slow waves