Pulsating contraction waves started from "the turning portion of the colon" in the rat and the guinea pig and propagated both orally as antiperistalsis and anally as peristalsis [1]. Hukuhara and Neya [1] named this portion the "pacemaker area." C-kit immunoreactive cells are known to be interstitial cells of Cajal (ICCs) and to generate pacemaker activity of the gastrointestinal tract [2,3]. Recently in the colonic "pacemaker area" [1] and in the proximal colon in guinea pig, a larger number of special smooth muscle cells corresponding to c-kit immunoreactive cells were found than in the distal colon [4]. We learned that tetrodotoxin (TTX)-insensitive rhythmic spontaneous contractions (RSCs) are present in the rat proximal colon and hypothesized that RSCs are generated and/or regulated by ICCs. To prove our hypothesis, we investigated whether these RSCs are absent in homozygous Ws/Ws mutant rats.A Ws/ϩ mutant rat with white spots and coat color dilution was first found in the inbred colony of the BN/fMai strain [5]. Because homozygous Ws/Ws rats were not obtained in the genetic background of BN/fMai strain, spotted BN/fMai-Ws/ϩ rats were crossed with ϩ/ϩ rats of the Donryu strain. Rats of -ATPase by cyclopiazonic acid (CPA) (10 Ϫ6 M) or by thapsigargin (10 Ϫ6 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 ϩ/ϩ 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.