Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

Abstract

The small intestine of W/Wv mice lacks both the network of interstitial cells of Cajal (ICC), associated with Auerbach's 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 Ca2+ channel blockers. W/Wv mice responded to K+ channel blockade (0.5 mM Ba2+ or 10 mM tetraethylammonium chloride) with effects on amplitude, frequency, rate of rise, and duration of the action potentials. In quiescent tissues from W/Wv mice, K+ channel blockade evoked the typical spikelike action potentials. Electron microscopy identified few methylene blue-positive cells in the W/Wv small intestine associated with Auerbach's plexus as individual ICC. Numbers of resident macrophage-like cells (MLC) and fibroblast-like cells (FLC) were significantly changed. Neither FLC nor MLC were part of a network nor did they form specialized junctions with neighboring cells as ICC do. Hence no cell type had replaced ICC at their normal morphological position associated with Auerbach's plexus. ICC 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 do not take part in generation of pacemaker activity.

Absence of peristalsis in the ileum of W/WV mutant mice that are selectively deficient in myenteric interstitial cells of Cajal

“…1B). These results are similar to those reported in previous studies (Malysz et al, 1996;Takayama et al, 2001Takayama et al, , 2002Nakagawa et al, 2005).…”

“…We have previously reported that spontaneous rhythmic contractions are observed in the proximal colon of Ws/Ws rats, where there is a deficiency of both ICC in the myenteric region (ICC-MY) and of ICC-SM (Yoneda et al, 2001). Furthermore, it has been reported that smooth muscle preparations of the small intestine (duodenum, jejunum or ileum) of W/W V mutant mice show a variety of electrical activities (Malysz et al, 1996), longitudinal cyclic contractions (Daniel et al, 2002) and distension-induced peristalsis . In the small intestine of W/W V mutant mice, while ICC-MY are absent, the ICC of the deep muscular plexus region (ICC-DMP) are present (Malysz et al, 1996;Takayama et al, 2001Takayama et al, , 2002.…”

“…Furthermore, it has been reported that smooth muscle preparations of the small intestine (duodenum, jejunum or ileum) of W/W V mutant mice show a variety of electrical activities (Malysz et al, 1996), longitudinal cyclic contractions (Daniel et al, 2002) and distension-induced peristalsis . In the small intestine of W/W V mutant mice, while ICC-MY are absent, the ICC of the deep muscular plexus region (ICC-DMP) are present (Malysz et al, 1996;Takayama et al, 2001Takayama et al, , 2002. Recent studies reported the presence of synapse-like contacts between enteric nerve terminals and intramuscular ICC (ICC-IM) in the stomach, where ICC-MY have been shown to be the pacemaker ICC (Ward et al, 2000(Ward et al, , 2004.…”

Co‐operation between neural and myogenic mechanisms in the control of distension‐induced peristalsis in the mouse small intestine

“…This indicates that the musculature can be directly activated by distension without mediation of enteric nerves. Activity in the presence of TTX or atropine was higher in WW v mice than in control mice, possibly because the musculature itself is depolarized and, hence, more excitable (Malysz, Thuneberg, Mikkelsen & Huizinga, 1996). With identical frequencies, the action potentials were synchronized and apparent propagation was observed ( Fig.…”

Local presentation of Steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture

“…ICC function as pacemaker cells in the gastrointestinal tract and may also modulate enteric neurotransmission (15,28,29). Spontaneous mutations at the white spotting locus, which encodes the c-kit receptor or the Steel locus, which encodes SF, are associated with disruption of the ICC network located at the myenteric plexus region (ICC-MY) of the small intestine and the functional loss of the spontaneous electrical slow wave and contractile activity (23,24,34,35). SF activation of c-kit is also necessary to maintain ICC, because the administration of neutralizing c-kit antibody results in the subsequent disappearance of ICC (21,30).…”