TRPC3: how current mechanistic understanding provides a basis for therapeutic targeting

Abstract

ABSTRACT Introduction Intensive and detailed investigations of the molecular function and cellular role of mammalian transient receptor potential canonical (TRPC) channels started back in the early 90th of the past century. Initial TRPC research was fueled by high hopes to resolve fundamental questions of cellular Ca2+ signaling. To date, we have learned important lessons in TRPC channel biology and biophysics while little progress has been made in terms of therapeutic concepts. Areas covered This is a critical account on recent progress in building a solid mechanistic basis for therapeutic interventions utilizing TRPC3 as a target. I focus on hurdles and key issues to be resolved, thereby drafting a list of essential scientific ‘to-dos’ on the way toward drugging of TRPC3. Expert opinion Recent advances in the molecular physiology of TRPC3 include unveiling its lipid sensing machinery and the channels´ ability to serve spatiotemporally diverse Ca2+ signaling in a cell type- and context-dependent manner. The ongoing development of technology for high-precision manipulation of the channel, opens up the view on novel therapeutic strategies. It is now to unravel the complex role of TRPC3 human physiopathology, to pinpoint the channels´ therapeutic relevance and to further refine technologies for targeted interventions.