Remarkable Progress with Small-Molecule Modulation of TRPC1/4/5 Channels: Implications for Understanding the Channels in Health and Disease

Aisling Minard; Claudia C Bauer; David J Wright; Hussein N Rubaiy; Katsuhiko Muraki; David J Beech; Robin S Bon

doi:10.3390/cells7060052

Remarkable Progress with Small-Molecule Modulation of TRPC1/4/5 Channels: Implications for Understanding the Channels in Health and Disease

Cells. 2018 Jun 1;7(6):52. doi: 10.3390/cells7060052.

Authors

Aisling Minard¹, Claudia C Bauer², David J Wright³, Hussein N Rubaiy⁴, Katsuhiko Muraki⁵, David J Beech⁶, Robin S Bon⁷

Affiliations

¹ School of Chemistry, University of Leeds, Leeds LS2 9JT, UK. cm10a3m@leeds.ac.uk.
² Department of Discovery and Translational Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK. c.bauer@leeds.ac.uk.
³ Department of Discovery and Translational Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK. d.j.wright1@leeds.ac.uk.
⁴ Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Hull HU6 7RX, UK. h.rubaiy@hull.ac.uk.
⁵ Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, Japan. kmuraki@dpc.agu.ac.jp.
⁶ Department of Discovery and Translational Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK. d.j.beech@leeds.ac.uk.
⁷ Department of Discovery and Translational Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK. r.bon@leeds.ac.uk.

Abstract

Proteins of the TRPC family can form many homo- and heterotetrameric cation channels permeable to Na⁺, K⁺ and Ca²⁺. In this review, we focus on channels formed by the isoforms TRPC1, TRPC4 and TRPC5. We review evidence for the formation of different TRPC1/4/5 tetramers, give an overview of recently developed small-molecule TRPC1/4/5 activators and inhibitors, highlight examples of biological roles of TRPC1/4/5 channels in different tissues and pathologies, and discuss how high-quality chemical probes of TRPC1/4/5 modulators can be used to understand the involvement of TRPC1/4/5 channels in physiological and pathophysiological processes.

Keywords: TRPC; calcium; chemical probes; ion channel; small molecules.

Publication types

Review

Grants and funding

MC_PC_17165/MRC_/Medical Research Council/United Kingdom