Coupling among interstitial cells of Cajal in the human ileum

Current knowledge on the morphology and physiology of interstitial cells of Cajal (ICC) is mostly based on animal studies, and information about the function of these cells in humans is scarce. There is ultrastructural evidence that ICC in the myenteric region (ICC-MP) of the small intestine of several species are connected by gap junctions, but these were not observed in the human small intestine. The aim of the present study was to determine whether functional coupling also exists among ICC-MP in the human ileum. We visualized ICC-MP in live tissues using Nomarski optics, and verified their identity by staining for c-Kit. ICC were injected intracellularly with the fluorescent dye Lucifer yellow, which crosses gap junctions. In most cases the labelled cells had oval somata with two primary processes. At normal pH (7.3-7.4) only 20.2% (21/104) of the injected ICC were coupled to other ICC. However, at pH 7.8-7.9 coupling incidence increased to 74.5% (35/47, P < 0.0001). The injected cells were coupled to one to 35 other ICC. Octanol blocked coupling in all cases. Apparently, gap junctions interconnect ICC in the human small intestine. Coupling was enhanced by a small increase in pH, suggesting that it may be under physiological control.