The Contribution of TRPC1 and STIM1 to Capacitative Ca2+ Entry in Pulmonary Artery

Capacitative calcium entry (CCE) through store-operated channels (SOCs) has been shown to contribute to the rise in intracellular calcium concentration ([Ca(2+)](i)) and mediate pulmonary artery smooth muscle contraction. CCE is activated as a result of depletion of intracellular Ca(2+) stores but there is a great deal of controversy surrounding the underlying signal that active CCE and the molecular makeup of SOCs. The discovery of canonical subgroup of transient receptor potential channels (TRPC) and recent identification of stromal-interacting molecule 1 (STIM1) protein have opened a door to the study of the identity of SOCs and the signal that activates these channels. Among all the TRPC channels, TRPC1 is widely studied in many cell types and shown to be part of SOCs components, whereas STIM1 protein is found to act as a Ca(2+) sensor in the intracellular Ca(2+) stores and activates SOCs. However, there is very little evidence for the roles of TRPC1 and STIM1 in the contribution of CCE in pulmonary artery. This chapter outlines the roles of TRPC1 and STIM1 in pulmonary artery smooth muscle cells and discusses our recent findings that TRPC1 and STIM1 are functionally interact with each other to mediate CCE in these cells. We also propose a model for the molecular makeup of SOCs formed by TRPC I and STIM1 in pulmonary artery.