Ca transients in ICC-MY define the basis for the dominance of the corpus in gastric pacemaking.

Myenteric interstitial cells of Cajal (ICC-MY) generate and actively propagate electrical slow waves in the stomach. Slow wave generation and propagation are altered in gastric motor disorders, such as gastroparesis, and the mechanism for the gradient in slow wave frequency that facilitates proximal to distal propagation of slow waves and normal gastric peristalsis is poorly understood.  Slow waves depend upon Ca-activated Cl channels (encoded by Ano1). We characterized Ca signaling in ICC-MY in situ using mice engineered to have cell-specific expression of GCaMP6f in ICC. Ca signaling differed in ICC-MY in corpus and antrum. Localized Ca transients were generated from multiple firing sites and were organized into Ca transient clusters (CTCs). Ca transient refractory periods occurred upon cessation of CTCs, but a relatively higher frequency of Ca transients persisted during the inter-CTC interval in corpus than in antrum ICC-MY. The onset of Ca transients after the refractory period was associated with initiation of the next CTC. Thus, CTCs were initiated at higher frequencies in corpus than in antrum ICC-MY. Initiation and propagation of CTCs (and electrical slow waves) depends upon T-type Ca channels, and durations of CTCs relied upon L-type Ca channels. The durations of CTCs mirrored the durations of slow waves. CTCs and Ca transients between CTCs resulted from release of Ca from intracellular stores and were maintained, in part, by store-operated Ca entry. Our data suggest that Ca release and activation of Ano1 channels both initiate and contribute to the plateau phase of slow waves.