Selective knockout of intramuscular interstitial cells reveals their role in the generation of slow waves in mouse stomach

Abstract

2. In wild-type mice interstitial cells were found at the level of the myenteric plexus (ICC MY ) and distributed within the smooth muscle bundles (ICC IM ). In these preparations slow waves, which consisted of initial and secondary components, were detected.3. In W/W V mutant mice ICC MY could be identified at the level of the myenteric plexus but ICC IM were not detected within smooth muscle bundles. Intracellular recordings revealed that smooth muscle cells generated waves of depolarization; these lacked a secondary component. These results indicate that the secondary regenerative component of a slow wave is generatedby ICC IM . Thus the depolarization arising from the pacemaker cells, ICC MY , is augmented by ICC IM , so causing a substantial membrane depolarization in the circular muscle layer. Rather than contributing directly to rhythmical electrical activity, smooth muscle cells appear to depolarize at the command of the two subpopulations of ICC.

Effects of RHC-80267, an Inhibitor of Diacylglycerol Lipase, on Excitation of Circular Smooth Muscle of the Guinea-Pig Gastric Antrum

“…IP3 may be also involved in the generation of slow potentials, but possibly downstream to PKC, as a determinant of the amplitude of slow potentials, through regulation of the amount of Ca 2+ released from the internal stores . The transient small fluctuations which appear in the interval between slow potentials may be propagated from ICC-IM through gap junctions (Dickens et al, 2001), and slow potentials may be the summed potentials of these fluctuating potentials (Edwards et al, 1999). These results allow speculation that the depolarization of the smooth muscle membrane is conducted to ICC-IM and evokes transient small fluctuations, possibly through activation of PKC.…”

“…The driving potential generated in ICC-MY is propagated to circular muscle cells to form a voltage-insensitive component of slow waves, and this potential triggers a voltage-sensitive component (Dickens et al, 1999). In gastric smooth muscle of W/W V mutant mice lacking ICC-IM, the caffeine-sensitive component of slow waves is absent, suggesting that this component is elicited by electrotonic spread of potentials generated in ICC-IM (Dickens et al, 2001).…”

Metabolic component of the temperature-sensitivity of slow waves recorded from gastric muscle of the guinea-pig

“…The addition of a slow potential to a pacemaker-derived electrotonic potential forms a slow wave (Tomita, 1999). Thus, slow waves comprise two components, the 1st component formed by a propagated pacemaker potential and the 2nd component formed by a slow potential generated in the circular muscle bundle (Dickens et al, 2001;Hirst and Edwards, 2001). Slow waves are absent in mice which lack expression of the inositol 1,4,5-trisphosphate (IP3) receptor, even in the presence of c-Kit positive interstitial cells , suggesting that the Ca 2+ releasing processes from internal stores through IP3 receptors take a key role in the generation of pacemaker potentials.…”

Effects of 5-hydroxytryptamine on electrical responses of circular smooth muscle isolated from the guinea-pig gastric antrum

“…Slow potentials can also be evoked by the membrane depolarization in an all or none fashion, with a refractory of 3-5 s Kito et al, 2002). In intact tissues with attached longitudinal muscle layer and ICC-MY, slow potentials generated in circular muscle layer form the 2nd component of slow waves (Dickens et al, 2001;Hirst et al, 2002;Hirst and Ward, 2003). Heterogeneous distribution of 5-hydroxytryptamine (5-HT) receptors in the gastrointestinal tissues suggests that 5-HT may be taking an important role for the digestive activity (Gershon, 2004).…”

“…The circular muscle segment produces ongoing small transient depolarizing potentials called unitary potentials, which are propagated electrical responses from interstitial cells of Cajal distributed within muscle bundles (ICC-IM) (Dickens et al, 2001). The frequency spectrum analysis of unitary potentials indicates that slow potentials are formed by a summation of unitary potentials generated in intramuscular interstitial cells of Cajal (ICC-IM) (Edwards et al, 1999).…”