Emerging Trends in Modulation of Transient Receptor Potential Canonical 6 Channels as Therapeutic Targets

Abstract

The transient receptor potential canonical (TRPC) channel family includes TRPC6, a nonselective receptor-activated cation channel. Its activation result in Ca2+, Na+ along with other cationic ion influx and the phosphorylation of tyrosine, serine and phosphoinositides regulates TRPC6. The channel is widely distributed and plays physiological role in different body parts such as kidney, lungs, blood vessels, heart, brain, intrinsic cardiac ganglia and eye. It has been determined that TRPC6 is a crucial part of the kidney podocytes. Mutation in TRPC6 gene results in focal segmental glomerulosclerosis. A significant function of TRPC6 is also witnessed in the pathogenesis of various cancers including breast, esophageal, renal, head and neck squamous cell carcinoma. TRPC6 channel is found to be overexpressed in the macrophages of chronic obstructive pulmonary disorder and has a role in cardiac hypertrophy. In last decade many natural, semi synthetic and synthetic pharmaceutical agents modulating TRPC6 activity have been investigated which can be alucrative approach for the prevention and treatment of diseases associated with TRPC6 channel downregulation and upregulation. Therefore, present review aims to summarize the involvement of TRPC6 with its Ca2+ dependent effect in different physiological and pathological conditions with the downregulation as well as upregulation of TRPC6 channel functions and summarizes the progress achieved in those investigations pertaining to modulators of TRP6 channels.