Electrical Communication Between Different Cell Types in the Colonic Musculature

Abstract

The major cell types in the canine colon musculature are interstitial cells of Cajal (ICC), circular muscle (CM) cells and longitudinal muscle (LM) cells. In isolated muscle strip studies, spontaneous membrane potential oscillations (slow waves) are generated in the submucosal border of the circular muscle where a gap junctionally well-coupled network of ICC and CM is found. CM devoid of LM and submucosal pacemaker region (CM preparations) are spontaneously quiescent. The research undertaken was to understand the mechanism of slow wave propagation into the circular muscle and to investigate the consequences to the electrical activity in CM after coupling with different electrical activities from different cells types. Our results show that CM cells, although spontaneously quiescent because of high K+ conductance, are excitable and can actively participate in slow wave generation. The electrical oscillations induced in the CM preparations could easily be potentiated by an L-type Ca2+ channel activator, Bay K 8644, and abolished by a L-type Ca2+ antagonist, D600, suggesting involvement of the conductance in the induced activity. The induced oscillations are similar to the SLAPs in the longitudinal muscle which shows that it is not necessary to have a specialized pacemaker cells for generating SLAPs. Using a cross sectioned preparation with all intact muscle layers, we also showed that the heterogeneity in the electrical activity of CM, such as: the resting membrane potential gradient, depolarization of plateau potential in the myenteric border and "apparent" decay in slow wave amplitude, is due to electrical interactions between different intrinsic activities from different cell types. Morphological evidence was obtained for the possible communication pathways in the submucosal and the myenteric borders of the circular muscle. Different coupling mechanisms in different areas were hypothesized. In addition, the 3-dimensional aspects of the submucosal ICC network in the ca.nine colon were clarified.