Neurotransmitter stimulation of fluid secretion in salivary glands is mediated via a biphasic elevation in cytosolic [Ca-2+]; an initial transient increase due to internal release and a latter sustained increase due to Ca-2+ influx. Sustained fluid secretion is suggested to directly dependent upon the sustained elevation of [Ca-2+]and thus on Ca-2+ influx. This project is aimed towards understanding the mechanisms which mediate and regulate Ca-2+ signaling in salivary gland cells. Recently, our efforts have been focused on the mechanisms involved in mediating and regulating Ca-2+ influx into salivary gland cells. Ca-2+ influx in salivary cells is prototypical of the store-operated Ca-2+ influx mechanism present in many other non-excitable cells. The molecular mechanism(s) of this influx has not yet been determined in any cell type. Recently, the transient receptor potential (Trp)family of ion channel proteins have been proposed as molecular components of the store-operated Ca-2+ influx channel. We have previously reported cloning of rat Trp1 and identification and localization of the endogenous Trp1 protein in rat and human salivary gland cells. In this reporting period we have further studied the role of Trp1 in the store-operated Ca-2+ influx mechanism. Our studies suggest that Trp1 is a strong candidate for the Ca-2+ influx channel in salivary gland cells. Further, we have reported that Trp1 is localized in a lipid raft region where it is assembled in a larger signaplex along with other Ca-2+ signaling molecules, such as the IP3R and G-proteins. salivary glands and human salivary gland cell lines. We propose that protein-protein interactions facilitated within this signaplex regulate store-operated Ca-2+ influx. Results from our functional studies where we have examined the Ca-2+ current mediated by the store-operated Ca-2+ channel by using patch clamp methodology, are also consistent with these findings. Our future studies will continue to focus on the store-operated Ca-2+ influx pathway, its regulation and role in salivary gland fluid secretion.
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