A novel intramuscular Interstitial Cell of Cajal is a candidate for generating pacemaker activity in the mouse internal anal sphincter

The internal anal sphincter (IAS) generates phasic contractions and tone. Slow waves (SWs) produced by interstitial cells of Cajal (ICC) underlie phasic contractions in other gastrointestinal regions. SWs are also present in the IAS where only intramuscular ICC (ICC-IM) are found, however the evidence linking ICC-IM to SWs is limited. This study examined the possible relationship between ICC-IM and SWs by recording Ca(2+) transients in mice expressing a genetically-encoded Ca(2+)-indicator in ICC (Kit-Cre-GCaMP6f). A role for L-type Ca(2+) channels (Cav(L)) and anoctamin 1 (ANO1) was tested since each is essential for SW and tone generation. Two distinct ICC-IM populations were identified. Type I cells (36% of total) displayed localised asynchronous Ca(2+) transients not dependent on Cav(L) or ANO1; properties typical of ICC-IM mediating neural responses in other gastrointestinal regions. A second novel sub-type, i.e., Type II cells (64% of total) generated rhythmic, global Ca(2+) transients at the SW frequency that were synchronised with neighbouring Type II cells and were abolished following blockade of either Cav(L) or ANO1. Thus, the spatiotemporal characteristics of Type II cells and their dependence upon Cav(L) and ANO1 all suggest that these cells are viable candidates for the generation of SWs and tone in the IAS.