Photopharmacology and opto-chemogenetics of TRPC channels-some therapeutic visions

Abstract

Non-selective cation conductances formed by transient receptor potential canonical (TRPC) proteins govern the function and fate of a wide range of human cell types. In the past decade, evidence has accumulated for a pivotal role of these channels in human diseases, raising substantial interest in their therapeutic targeting. As yet, an appreciable number of small molecules for block and modulation of recombinant TRPC conductances have been identified. However, groundbreaking progress in TRPC pharmacology towards therapeutic applications is lagging behind due to incomplete understanding of their molecular pharmacology and their exact role in disease. A major breakthrough that is expected to overcome these hurdles is the recent success in obtaining high-resolution structure information on TRPC channel complexes and the advent of TRP photopharmacology and optogenetics. Here, we summarize current concepts of enhancing the precision of therapeutic interference with TRPC signaling and TRPC-mediated pathological processes.

Keywords: Chemogenetic manipulation; Photochromic ligands; Photopharmacology; TRPC channels; TRPC pathophysiology.