Gastrointestinal motility disorders constitute a substantial problem in the horse both in
terms of welfare and economic cost. It is often difficult to identify the underlying cause
as many horses recover spontaneously or with empirical medical treatment. Recently,
the gastrointestinal pacemaker cells, the interstitial cells of Cajal (ICC), were identified
in the horse. These cells initiate and coordinate gastrointestinal motility patterns through
the generation of slow waves. This current study investigated the ICC in the equine
intestine both in health and disease using immunohistochemical, electrophysiological
and molecular biological techniques. The aim of these studies was to further our
knowledge on the role of ICC in equine intestinal motility disorders.Using immunohistochemistry targeting a receptor tyrosine kinase, c-Kit, of the ICC, the
ontogeny of these cells in the horse was described. This demonstrated a proximal to
distal, as well as a transmural developmental gradient in the large intestine with
evidence of ongoing postnatal development. Additionally, the density of ICC in healthy,
adult horses was compared to that in horses with obstructive intestinal disease requiring
surgical correction. This demonstrated a significant reduction in ICC density in horses
with obstructive disorders of the large intestine compared to the control group. In
addition, ICC density and distribution was investigated in recovered chronic equine
grass sickness horses as well as in normal and diseased donkeys.The c-kit gene, encoding the c-Kit receptor of the ICC, was identified in intestinal tissue
samples. The transcription levels of this gene were determined and comparisons made
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between healthy and diseased horses using quantitative real-time PCR analysis. A
parallel immunohistochemical assessment was also performed. These studies
demonstrated no significant changes in gene transcription levels, although a reduction in
ICC density (using c-Kit immunohistochemistry) in horses with an obstructive disorder
of the large colon was evident, suggesting that future investigations of c-kit posttranscriptional control as well as c-Kit protein pathology are warranted.Investigation of the in vitro electrical activity of the equine large colon was carried out
using intracellular microelectrode recording techniques in order to characterise slow
waves and other electrical activities in this anatomical region from normal and diseased
horses.It is hoped that this study will help improve our knowledge ofthe involvement of ICC in
equine intestinal motility in health and disease. Furthermore, it may facilitate future
studies investigating the involvement and function of the ICC in the equine
gastrointestinal tract
