Work

TRPC3 and TRPC6: Multimodal Cation-Conducting Channels Regulating Cardiovascular Contractility and Remodeling

Year: 2026

Type: article

Abstract: Transient receptor potential canonical (TRPC) channels function as multimodal cation channels that integrate chemical and mechanical cues to regulate cellular signaling. Among them, TRPC3 and TRPC6 have been studied primarily in the context of cardiovascular and renal physiology, and their roles in other organ systems are now increasingly recognized. Although these channels are known to be activated downstream of phospholipase C (PLC) signaling, especially 1,2-diacylglycerol (DAG) production, their precise modes of activation under native physiological conditions remain incompletely understood. Recent structural and functional studies have greatly advanced our understanding of their primary activation by DAG. This review summarizes how decades of physiological analyses have revealed multiple modes of TRPC3 and TRPC6 channel activation beyond DAG gating, providing a broader perspective on their diverse regulatory mechanisms. This review also highlights recent progress in elucidating the channel properties, activation mechanisms, and the physiological as well as pathophysiological roles of TRPC3 and TRPC6 in cardiovascular contractility and remodeling, and discusses the remaining challenges that will lead to the establishment of TRPC3 and TRPC6 as validated therapeutic targets.

Source: Cells

DOI: 10.3390/cells15020144

Authors: Takuro Numaga-Tomita, Motohiro Nishida

Institutions: Shinshu University, Kyushu University, National Institutes of Natural Sciences, National Institute for Physiological Sciences, The Exploratory Research Center on Life and Living Systems

Language: English

Topic: Ion Channels and Receptors

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258