Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

• DOI: 10.1073/pnas.1308963111
• Publication Date: 2014-01-23T03:42:30Z
• Authors: Kinya Seo; Peter P. Rainer; Virginia Shalkey ...; Dong-ik Lee; Su-Hyun Jo; Asger Andersen; Ting Liu; Xiaoping Xu; Robert N. Willette; John J. Lepore; Joseph P. Marino; Lutz Birnbaumer; Christine G. Schn...; David A. Kass
• Keywords: TRPC3; TRPC6; Pressure overload

Significance Cardiac hypertrophy and dysfunction in response to sustained hormonal mechanical stress are sentinel features of most forms heart disease. Activation non–voltage-gated transient receptor potential canonical channels TRPC3 TRPC6 may contribute this pathophysiology provide a therapeutic target. Effects from combined selective inhibition have not been tested previously. Here we report the capability highly TRPC3/6 inhibitors block pathological hypertrophic signaling several cell types, including adult cardiac myocytes. We show vivo redundancy each channel; individual gene deletion was protective against pressure overload, whereas ameliorated response. These data strongly support role for both disease utility inhibition.