Does ICC pacing require functional gap junctions between ICC and smooth muscle in mouse intestine?

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.