TRPC Channels: Prominent Candidates of Underlying Mechanism in Neuropsychiatric Diseases.

Alterations in intracellular Ca(2+) concentration ([Ca(2+)]i) play a crucial role in fundamental cellular events from transcriptional regulation to migration and proliferation. The transient receptor potential (TRP) channels contribute to changes in [Ca(2+)]i by providing or modulating Ca(2+) entry pathways, as well as by releasing Ca(2+) from intracellular stores. On the basis of sequence homology, the TRP family can be divided into seven subfamilies: the TRPC ("canonical") family, the TRPV ("vanilloid") family, the TRPM ("melastatin") family, the TRPP ("polycystin") family, the TRPML ("mucolipin") family, the TRPA ("ankyrin") family, and the TRPN ("NOMPC") family. In this review, we focus on the physiology and pathophysiology of mammalian TRPC channels in the nervous system. Seven mammalian TRPC proteins (TRPC1-7) have been described and are widely distributed in the brain from early embryonic days till adulthood, with the exception of TRPC2. TRPC channels are nonselective Ca(2+)-permeable channels, which can be activated by G-protein-coupled receptors and receptor tyrosine kinases. These channels have been reported to act as essential cellular sensors in multiple processes during neuronal development, including neural stem cell proliferation and differentiation, neuronal survival, neurite outgrowth and axon path finding, and synaptogenesis. Not surprisingly, studies on these channels also provide new insights into underlying mechanisms of various neuropsychiatric disorders. The present review summarizes the expressions of all TRPC subtypes in different brain regions and different neural cell types, aiming to serve as a useful reference for future studies in this field. We also discuss the most updated evidence implicating involvement of TRPC channels in the generation of pathophysiological states in nervous system and their potentials as being promising targets for drug development.