Connexin43 expression in network-forming cells at the submucosal-muscular border of guinea pig and dog colon.

The tissue-specific expression of connexin subtypes in gap junctions between the interstitial cells and smooth muscle cells in the submuscular plexus of the colon has a functional importance in relation to intestinal pacemaker activity. Immunocytochemical observations of two types of connexin molecules, connexin43 and connexin45, were made with a confocal laser scanning microscope on cryosections of freshly frozen dog, guinea pig, mouse and rat proximal colon. Connexin43 immunoreactivity appeared as a series of dots along the submuscular plexus of guinea pig and dog. In contrast, connexin43 immunoreactivity was not found in mouse and rat colon. Connexin43 immunoreactivity was not observed in the colon muscular layer in the four animal species examined. In double-stained materials with a marker for either vimentin or smooth muscle actin, connexin43 immunoreactivity was colocalized with vimentin immunoreactivity, whereas it was not with either smooth muscle actin immunoreactivity or phalloidin reactivity. This indicated that the connexin43-expressing cells possess a vimentin-positive fibroblast-like nature rather than a smooth muscle-like one. In addition, in guinea pig colon, connexin43 immunoreactivity colocalized with c-Kit immunoreactivity. In conclusion, network-forming cells are connected by connexin43 gap junctions in the submuscular plexus of guinea pig and dog colon, most likely indicating that interstitial cells act as an intestinal pacemaker and conductive system.