Regional variation in contribution of myenteric and intramuscular interstitial cells of Cajal to generation of slow waves in mouse gastric antrum (original) (raw)
Related papers
The Journal of Physiology, 2003
Phase advancement of electrical slow waves and regulation of pacemaker frequency was investigated in the circular muscle layer of the gastric antra of wild-type and W/W V mice. Slow waves in the murine antrum of wild-type animals had an intrinsic frequency of 4.4 cycles min _1 and were phase advanced and entrained to a maximum of 6.3 cycles min _1 using 0.1 ms pulses of electrical field stimulation (EFS) (three pulses delivered at 3-30 Hz). Pacing of slow waves was blocked by tetrodotoxin (TTX) and atropine, suggesting phase advancement was mediated via intrinsic cholinergic nerves. Phase advancement and entrainment of slow waves via this mechanism was absent in W/W V mutants which lack intramuscular interstitial cells of Cajal (ICC-IM). These data suggest that neural regulation of slow wave frequency and regulation of smooth muscle responses to slow waves are mediated via nerve-ICC-IM interactions. With longer stimulation parameters (1.0-2.0 ms), EFS phase advanced and entrained slow waves in wild-type and W/W V animals. Pacing with 1-2 ms pulses was not inhibited by TTX or atropine. These data suggest that stimulation with longer pulse duration is capable of directly activating the pacemaker mechanism in ICC-MY networks. In summary, intrinsic excitatory neurons can phase advance and increase the frequency of antral slow waves. This form of regulation is mediated via ICC-IM. Longer pulse stimulation can directly activate ICC-MY in the absence of ICC-IM.
Interstitial cells of Cajal generate electrical slow waves in the murine stomach
The Journal of Physiology, 1999
Interstitial cells of Cajal (ICC) are small spindle-shaped or stellate cells with numerous mitochondria and long processes that form networks between and within smooth muscle layers in the gastrointestinal (GI) tract (Thuneberg, 1982; Sanders, 1996). Populations of ICC are found in pacemaker regions of gastrointestinal muscles (Suzuki et al. 1986; Berezin et al. 1988). Isolated ICC are electrically rhythmic and express ionic conductances consistent with a role in pacemaking (Langton et al. 1989; Lee & Sanders, 1993). More recent studies have shown that ICC retain electrical rhythmicity in culture via generation of spontaneous transient inward currents (
AJP: Gastrointestinal and Liver Physiology, 2009
Lammers WJ, Ver Donck L, Stephen B, Smets D, Schuurkes JA. Origin and propagation of the slow wave in the canine stomach: the outlines of a gastric conduction system. Slow waves are known to originate orally in the stomach and to propagate toward the antrum, but the exact location of the pacemaker and the precise pattern of propagation have not yet been studied. Using assemblies of 240 extracellular electrodes, simultaneous recordings of electrical activity were made on the fundus, corpus, and antrum in open abdominal anesthetized dogs. The signals were analyzed off-line, pathways of slow wave propagation were reconstructed, and slow wave velocities and amplitudes were measured. The gastric pacemaker is located in the upper part of the fundus, along the greater curvature. Extracellularly recorded slow waves in the pacemaker area exhibited large amplitudes (1.8 Ϯ 1.0 mV) and rapid velocities (1.5 Ϯ 0.9 cm/s), whereas propagation in the remainder of the fundus and in the corpus was slow (0.5 Ϯ 0.2 cm/s) with low-amplitude waveforms (0.8 Ϯ 0.5 mV). In the antrum, slow wave propagation was fast (1.5 Ϯ 0.6 cm/s) with large amplitude deflections (2.0 Ϯ 1.3 mV). Two areas were identified where slow waves did not propagate, the first in the oral medial fundus and the second distal in the antrum. Finally, recordings from the entire ventral surface revealed the presence of three to five simultaneously propagating slow waves. High resolution mapping of the origin and propagation of the slow wave in the canine stomach revealed areas of high amplitude and rapid velocity, areas with fractionated low amplitude and low velocity, and areas with no propagation; all these components together constitute the elements of a gastric conduction system.
American journal of physiology. Gastrointestinal and liver physiology, 2015
Slow waves (slow wavesICC) were recorded from myenteric interstitial cells of Cajal (ICC-MY) in situ in the rabbit small intestine, and their properties were compared with those of mouse small intestine. Rabbit slow wavesICC consisted of an upstroke depolarization followed by a distinct plateau component. Ni(2+) and nominally Ca(2+)-free solutions reduced the rate-of-rise and amplitude of the upstroke depolarization. Replacement of Ca(2+) with Sr(2+) enhanced the upstroke component but decreased the plateau component of rabbit slow wavesICC. In contrast, replacing Ca(2+) with Sr(2+) decreased both components of mouse slow wavesICC. The plateau component of rabbit slow wavesICC was inhibited in low-extracellular-Cl(-)-concentration (low-[Cl(-)]o) solutions and by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl(-) channels, cyclopiazonic acid (CPA), an inhibitor of internal Ca(2+) pumps, or bumetanide, an inhibitor of Na(+)-K(+)-2Cl(-) cotransporter...
The pacemaker activity of interstitial cells of Cajal and gastric electrical activity
Physiological research / Academia Scientiarum Bohemoslovaca, 2003
Interstitial cells of Cajal (ICC) are the pacemaker cells in the gut. They have special properties that make them unique in their ability to generate and propagate slow waves in gastrointestinal muscles. The electrical slow wave activity determines the characteristic frequency of phasic contractions of the stomach, intestine and colon. Slow waves also determine the direction and velocity of propagation of peristaltic activity, in concert with the enteric nervous system. Characterization of receptors and ion channels in the ICC membrane is under way, and manipulation of slow wave activity markedly alters the movement of contents through the gut. Gastric myoelectrical slow wave activity produced by pacemaker cells (ICC) can be reflected by electrogastrography (EGG). Electrogastrography is a perspective non-invasive method that can detect gastric dysrhythmias associated with symptoms of nausea or delayed gastric emptying.
Generation and propagation of gastric slow waves
Clinical and Experimental Pharmacology and Physiology, 2010
Mechanisms underlying the generation and propagation of gastrointestinal sloww av e depolarizations have long been controversial. This reviewa ims to collate present knowledge on this subject with specific reference to slowwav esingastric smooth muscle.
Distribution of pacemaker function through the tunica muscularis of the canine gastric antrum
The Journal of Physiology, 2001
Interstitial cells of Cajal (ICC) are found at specific locations within the tunica muscularis of the gastrointestinal (GI) tract. Studies performed on tissues of the mouse and guinea-pig have suggested that ICC in different anatomical locations have discrete physiological roles. Studies in the mouse have been aided by the fact that ckit and stem cell factor mutant animals fail to develop certain types of ICC, and specific functional losses have been observed in these animals (Ward et al. 1994, 1995; Huizinga et al. 1995; Burns et al. 1996). For example, when ICC in the myenteric region of the small intestine (IC-MY) are lost, slow wave activity is not present, suggesting that IC-MY are pacemaker cells (Ward et al. 1994; Huizinga et al. 1995). When intramuscular ICC of the stomach and lower oesophageal and pyloric sphincters are lost, neural inputs from the enteric nervous system are greatly reduced, suggesting these cells are important mediators of neurotransmission (Burns et al. 1996; Ward et al. 1998, 2000a). Studies with neutralizing antibodies to Kit protein have supported the idea that IC-MY are pacemaker cells (Torihashi et al. 1995) and demonstrated that these cells are also needed for active propagation of slow waves in the small bowel and stomach (Ordog et al. 1999). Thus, a picture has emerged regarding the functional significance of ICC in the GI tract, and these studies have suggested that a 'division of labour' exists between pacemaker ICC (IC-MY) and ICC involved in neurotransmission (IC-IM in the stomach and IC-DMP in the small intestine: see Sanders et al. 1999). The concept that electrical slow waves originate in ICC, actively propagate in ICC, and passively spread into electrically coupled smooth muscle cells is supported by