Rhythmic spontaneous contractions in the rat proximal colon

C-kit immunoreactive cells are known to be interstitial cells of Cajal (ICCs), and they generate pacemaker activity of the gastrointestinal tract. Recently a large number of special smooth muscle cells corresponding to c-kit immunoreactive cells were found in the proximal colon of the guinea pig. We learned that the rat proximal colon showed tetrodotoxin-insensitive regular rhythmic spontaneous contractions (RSCs) and hypothesized that RSCs are generated and/or regulated by ICCs. To prove our hypothesis, we investigated whether RSCs are absent in homozygous Ws/Ws mutant rats, since c-kit positive ICCs along the submucosal surface of the circular muscle (ICC_SM) and myenteric plexus (ICC_MY) are lacking. In contrast to our hypothesis, we found that RSCs were still present in the proximal colon of the Ws/Ws mutant rats. A recent study has reported that c-kit negative ICC_SM remains in Ws/Ws mutant rats. Taken together, RSCs may be generated by c-kit negative ICC_SM in the rat proximal colon. The blockade of sarcoplasmic reticulum Ca²⁺-ATPase by cyclopiazonic acid (CPA) (10^-6M) or by thapsigargin (10^-6 M) increased the frequency of RSCs. The increasing effects of CPA on the frequency of RSCs were more prominent in Ws/Ws mutant rats than in +/+ rats. We concluded that the functional coordination between c-kit negative ICC_SM and other mutationally impaired c-kit positive ICC_MY and ICC_SM may be required for moderate regulation in the frequency of spontaneous activity.