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Updated: May 5, 2026
Visualization of the Interstitial Cells of Cajal ICC Network in Mice
Published on: July 27, 2011
Heterogeneities in ICC Ca2+ activity within canine large intestine
Hyun-Tai Lee1, Grant W Hennig, Kyu Joo Park
1Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA.
Insights
Interstitial cells of Cajal at the submucosal border (ICC-SM) generate slow waves, while those at the myenteric border (ICC-MY) produce faster rhythms similar to myenteric potential oscillations (MPOs). ICC-SMs form a coupled network, whereas ICC-MY activity is modulated by nerve input.
Area of Science:
- Gastroenterology
- Physiology
- Cell Biology
Background:
- The colon exhibits distinct electrical rhythms: slow waves (2-8/min) and myenteric potential oscillations (MPOs; 16-20/min).
- These rhythms originate from specific locations within the smooth muscle layers.
- Interstitial cells of Cajal (ICCs) are known pacemakers in the gastrointestinal tract.
Purpose of the Study:
- To investigate whether ICCs at the submucosal and myenteric borders generate distinct electrical rhythms.
- To characterize the properties of Ca(2+) signaling in ICCs from these different locations.
Main Methods:
- Utilized Ca(2+) imaging in canine colon segments.
- Monitored intracellular Ca(2+) activity in ICCs at submucosal (ICC-SM) and myenteric (ICC-MY) borders.
- Employed an electron multiplying charge coupled device (EMCCD) for high-resolution imaging.
Main Results:
- ICC-SMs exhibited rhythmic Ca(2+) transients (5-8/min) propagating as waves, consistent with slow waves.
- ICCs at the myenteric border (ICC-MY) displayed faster Ca(2+) waves (approx. 16/min) and spontaneous Ca(2+) reductions.
- Nitric oxide antagonism increased ICC-MY wave frequency, while nerve activity modulated synchronization.
Conclusions:
- ICC-SMs form a tightly coupled network responsible for generating and propagating slow waves.
- ICC-MYs exhibit Ca(2+) transients with frequencies similar to MPOs, influenced by neural input.
- These findings differentiate the roles of ICCs at distinct colonic borders in generating electrical rhythms.
Background & Aims:
In human and canine colon, both slow (slow waves, 2-8/min) and fast (myenteric potential oscillations [MPOs]; 16-20/min) electrical rhythms in the smooth muscle originate at the submucosal and myenteric borders, respectively. We used Ca(2+) imaging to investigate whether interstitial cells of Cajal (ICCs) at these borders generated distinct rhythms.
Methods:
Segments of canine colon were pinned with submucosal or myenteric surface uppermost or cut in cross section. Tissues were loaded with a Ca(2+) indicator (fluo-4), and activity was monitored at 36.5 +/- 0.5 degrees C using an electron multiplying charge coupled device (EMCCD).
Results:
Rhythmic, biphasic Ca(2+) transients (5-8/min), similar in waveform to electrical slow waves, propagated without decrement as a wave front (2-5 mm/s) through the ICC-SM network lying along the submucosal surface of the circular muscle (CM). In contrast, rhythmic intracellular Ca(2+) waves (approximately 16/min) and spontaneous reductions in Ca(2+) were observed in ICCs at the myenteric border (ICC-MY). Normally, intracellular Ca(2+) waves were unsynchronized between adjacent ICC-MY, although excitatory nerve activity synchronized activity. In addition, spontaneous reductions in Ca(2+) were observed that inhibited Ca(2+) waves. N omega-nitro-L-arginine (100 micromol/L; nitric oxide antagonist) blocked the reductions in Ca(2+) and increased the frequency (approximately 19/min) of intracellular Ca(2+) waves within ICC-MY.
Conclusions:
ICC-SMs form a tightly coupled network that is able to generate and propagate slow waves. In contrast, Ca(2+) transients in ICC-MYs, which are normally not synchronized, have a similar duration and frequency as MPOs. Like MPOs, their activity is inhibited by nitrergic nerves and synchronized by excitatory nerves.
