Role of store-operated Ca entry mechanism in signal transduction in gastrointestinal intrinsic neurons

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The aim of this project was to identify the regulatory mechanisms of capacitative Ca entry in gastrointestinal intrinsic neurons. For these purposes, we analyzed the properties of capacitative Ca entry, its regulatory mechanisms with intracellular messengers and putative channel molecules. 1) We established experimental system for visualization of Ca signaling in single cultured gastrointestinal intrinsic neurons. 2) ATP elicited Ca increases through release of Ca from intracellular stores, the activation of capacitative Ca entry and P2X2 channels in rat cultured gastrointestinal intrinsic neurons. 3) Bradykinin evoked the elevation of Ca through B2 receptor activation on gastrointestinal intrinsic neurons via PGE2 secreted from enteric glial cells. 4) Cloned TRPC5 channels expressed in PC12 cells functioned as Ca entry channels coupled with GTP-binding protein receptors. 5) Complimentary DNA for TRPV1 was cloned and was hetelogeously expressed in HEK293 cells. We revealed that TRPV1 channels functioned as polymodal receptor channels with high Ca permeability. These results indicate that capacitative Ca entry channels play a role for functional Ca entry pathways in gastrointestinal intrinsic neurons, which are regulated by various intrinsic factors such as ATP and bradykinin. Cloned TRPC5 and TRPV1 constitute Ca entry channels for regulation of intracellular Ca signallings.