IngentaConnect Action potential generation, Kit receptor immunohistochemistry an...

Abstract:

In contrast to wild-type mice, homozygotes with mutations of the W locus do not express the functional Kit receptor and are severely deficient in the Auerbach's plexus (AP)-associated subtype of interstitial cells of Cajal (ICC-AP). With a morphologically intact neural and muscular structure, the absence in these mutants of both small-intestinal slow waves and ICC-AP constitutes strong evidence for a key role of ICC-AP as pacemaker cells. In steel-Dickie mutant mice (Sl/Sl^d), the gene coding for the Kit ligand (stem cell factor) is defective. We examined Sl/Sl^d mutants and controls with intracellular microelectrode techniques, combined with light and electron microscopy. The absence of the normal Kit ligand (Sl/Sl^d mice) had very similar effects as the absence of the Kit receptor in viable mice, mutated at the White spotting, W, locus (W/W^v mice), in that neither slow waves, nor Kit receptor immunoreactivity in the region of Auerbach's plexus nor ICC-AP were present in the small intestine. In the Sl/Sl^d mouse, the smooth muscle cells generated action potentials at variable frequencies from a depolarized cell membrane of – 40 to – 55 mV. Increasing excitability by K channel blockers created many different patterns of action potential generation and the frequency increased from sim 16 cpm to 66 cpm. This was in sharp contrast to control mice where action potentials were always restricted to the plateau phase of the slow waves and the slow wave frequency remained constant at sim 39 cpm. Our data provide further strong support for the identification of ICC-AP as small-intestinal pacemaker cells. In addition, they provide a basis for the understanding of intestinal motor function without pacemaker activity.

Keywords: interstitial cells of Cajal; mouse; pacemaker; small intestine; steel mutation

Language: English

Document Type: Research article

Affiliations: 1: Institute of Medical Anatomy, The Panum Building, University of Copenhagen, DK-2200 Copenhagen N, Denmark 2: Intestinal Disease Program and Department of Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada *

Action potential generation, Kit receptor immunohistochemistry and morphology of steel-Dickie (Sl/Sld) mutant mouse small intestine

Action potential generation, Kit receptor immunohistochemistry and morphology of steel-Dickie (Sl/Sl^d) mutant mouse small intestine