Action potential generation in the small intestine of w mutant mice
that lack interstitial cells of cajal.
Malysz, John, Lars Thuneberg, Hanne B. Mikkelsen, and Jan D. Huizinga.
Intestinal Disease Research Programme and Department of Biomedical
Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada and
Institute for Medical Anatomy, Panum Institute, University of
Copenhagen, DK-2000 Copenhagen, Denmark
APStracts 3:0030G, 1996.
The small intestine of W/Wv mice lacks both the network of
interstitial cells of Cajal associated with the myenteric plexus, and
pacemaker activity, i.e. it does not generate slow wave type action
potentials. The W/Wv muscle preparations showed a wide variety of
electrical activities ranging from total quiescence to generation of
action potentials at regular or irregular frequency with or without
periods of quiescence. The action potentials consisted of a slow
component with superimposed spikes, preceded by a slowly developing
depolarization and followed by a transient hyperpolarization. The
action potentials were completely abolished by L-type calcium channel
blockers. W/Wv mice responded to K+ channel blockade (0.5 mM Ba2+ or
10 mM TEA) with effects on amplitude, frequency, rate of rise, and
duration of the slow component. In quiescent tissues from W/Wv mice,
K+ channel blockade evoked the typical spike like action potentials.
Electron microscopy identified few methylene blue positive cells in
the W/Wv small intestine associated with Auerbach's plexus as
individual interstitial cells of Cajal. Numbers of resident
macrophages (MLC) and fibroblast-like cells (FLC) were significantly
changed. Neither FLC not MLC were part of a network nor did they form
specialized junctions with neighbouring cells as ICC do. Hence, no
cell type had replaced interstitial cells of Cajal at their normal
morphological position associated with Auerbach's plexus.
Interstitial cells of Cajal were present in W/Wv mice at the deep
muscular plexus in normal organization and numbers indicating that
they are not dependent on the Kit protein and these ICC do not take
part in generation of pacemaker activity.
Received 25 August 1995; accepted in final form 22 January 1996.
APS Manuscript Number G370-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96