Transient receptor potential canonical 6 channel (TRPC6)

The transient receptor potential canonical 6 channel (TRPC6) is a member of the TRP channel superfamily, structurally characterized by six transmembrane domains and intracellular N- and C-termini with ankyrin repeats and regulatory regions. TRPC6 forms tetrameric complexes and functions as a receptor-operated, calcium-permeable nonselective cation channel, with a strong preference for calcium over sodium ions (P_Ca/P_Na ≈ 6). It is gated directly by diacylglycerol (DAG), linking phospholipase C-coupled receptor activation to ion channel activity. TRPC6 channels are widely expressed in kidney, heart, brain, lung, and other tissues, regulating essential physiological functions such as calcium signaling, actin cytoskeleton dynamics, cell proliferation, and mechanical force transduction. Dysregulation of TRPC6 is implicated in several diseases including glomerular kidney diseases, cardiac hypertrophy, neurological disorders, and certain cancers, making it an appealing therapeutic target for drug development. Multiple drugs, both antagonists and agonists, act on TRPC6 by modulating its gating and permeability, with BTDM as a notable example of a high-affinity inhibitor. Genetic mutations, overexpression, and functional activity of TRPC6 serve as important biomarkers in disease contexts, but modulation of TRPC6 carries notable safety concerns due to its central role in Ca^2+-dependent signaling processes throughout the body.

Other names

TRPC6Transient receptor potential channel 6Transient receptor potential cation channel, subfamily C, member 6

Direct inhibition of channel gating by antagonists (e.g., BTDM); Modulation of calcium influx to affect downstream signaling pathways, such as calcineurin/NFAT