Canonical transient receptor potential 4 and its small molecule modulators.

Canonical transient receptor potential 4 (TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca(2+) entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases. Moreover, the channels are regulated by pertussis toxin-sensitive Gi/o proteins, lipids, and various other signaling mechanisms. TRPC4-containing channels participate in the regulation of a variety of physiological functions, including excitability of both gastrointestinal smooth muscles and brain neurons. This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels.