TRPC channels: Structure, function, regulation and recent advances in small molecular probes

Publication date: Available online 28 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Hongbo Wang, Xiaoding Cheng, Jinbin Tian, Yuling Xiao, Tian Tian, Fuchun Xu, Xuechuan Hong, Michael X. ZhuAbstractTransient receptor potential canonical (TRPC) channels constitute a group of receptor-operated calcium-permeable nonselective cation channels of the TRP superfamily. The seven mammalian TRPC members, which can be further divided into four subgroups (TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7) based on their amino acid sequences and functional similarities, contribute to a broad spectrum of cellular functions and physiological roles. Studies have revealed complexity of their regulation involving several components of the phospholipase C pathway, Gi and Go proteins, and internal Ca2+ stores. Recent advances in cryogenic electron microscopy have provide several high-resolution structures of TRPC channels. Growing evidence demonstrates the involvement of TRPC channels in diseases, particularly the link between genetic mutations of TRPC6 and familial focal segmental glomerulosclerosis. Because TRPCs were discovered by the molecular identity first, their pharmacology had lagged behind. This is rapidly changing in recent years owning to great efforts from both academia and industry. A number of potent tool compounds from both synthetic and natural products that selective target different subtypes of TRPC channels have been discovered, including some preclinical drug candidates. This...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research