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Updated: Aug 8, 2026
Visualization of the Interstitial Cells of Cajal (ICC) Network in Mice
Published on: July 27, 2011
Does ICC pacing require functional gap junctions between ICC and smooth muscle in mouse intestine?
T Schultz1, V Daniel, E E Daniel
1Department of Pharmacology, University of Alberta, Edmonton, Canada.
Insights
Interstitial cells of Cajal (ICC) likely pace mouse intestinal circular muscle via gap junctions. Carbenoxolone, a gap junction inhibitor, affected longitudinal muscle contractility but primarily impacted circular muscle pacing.
Area of Science:
- Gastroenterology
- Physiology
- Cell Biology
Background:
- Interstitial cells of Cajal (ICC) are crucial for gastrointestinal motility.
- The precise role of gap junctions in ICC-mediated muscle pacing remains under investigation.
Purpose of the Study:
- To investigate the role of gap junctions in ICC-driven pacing of longitudinal and circular smooth muscle in the mouse intestine.
- To determine if carbenoxolone affects muscle contractility independently of gap junction inhibition.
Main Methods:
- Isolated mouse intestinal muscle segments were treated with tetrodotoxin and L-NOARG to block nerve function.
- Carbenoxolone, a gap junction inhibitor, was applied at varying concentrations and times.
- Muscle contraction amplitude and frequency were measured.
- Responses to electrical field stimulation were assessed.
- Tonic contractions induced by high KCl were evaluated.
Main Results:
- Carbenoxolone dose- and time-dependently inhibited contraction amplitude in longitudinal muscle but not frequency.
- Carbenoxolone inhibited contraction amplitude and slightly reduced frequency in circular muscle.
- Carbenoxolone inhibited tonic contractions in longitudinal muscle, suggesting direct effects.
- Electrical field stimulation responses were not significantly affected in either muscle type after nerve blockade.
Conclusions:
- Gap junctions within the circular muscle are likely involved in ICC-mediated pacing.
- Carbenoxolone exhibits direct inhibitory effects on longitudinal muscle contractility.
- Further research is needed to fully elucidate the role of gap junctions in intestinal smooth muscle physiology.
Abstract:
We tested the hypothesis that interstitial cells of Cajal (ICC) pace longitudinal and circular muscle of mouse intestine through gap junctions. Carbenoxolone (10(-6), 10(-5), 10(-4) mol L(-1)), an inhibitor of gap junction conductance, was applied to segments of longitudinal or circular muscle with contractions driven by ICC after inhibition of nerve function by tetrodotoxin (10(-6) mol L(-1)) and L-NOARG (10(-4) mol L(-1)). Carbenoxolone concentration- and time-dependently inhibited the amplitude of contraction (0.2-1.5 g in controls) of segments of longitudinal muscle, but had no effect on the frequency of contractions (from 36-54 min). It also inhibited the amplitude of contractions of circular muscle segments and reduced the frequency slightly at 10(-4) mol L(-)1. Carbenoxolone inhibited tonic contractions of longitudinal but not circular segments to 60 mmol L(-1) KCl, suggesting that it directly inhibited contractions of longitudinal muscle. The responses to pacing by electrical field stimulation (40 V cm(-1), 50-100 ms, 1 Hz) after block of nerve function were reduced insignificantly in amplitude, and not in frequency in both longitudinal and circular segments. We conclude that it is likely that only gap junctions within circular muscle are involved in pacing of muscle by ICC. Carbenoxolone also has effects on muscle contractility in longitudinal muscle.
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