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(Circulation Research. 2006;99:119.)
© 2006 American Heart Association, Inc.

Review

Transient Receptor Potential Channels in Cardiovascular Function and Disease

Ryuji Inoue, Lars Jørn Jensen, Juan Shi, Hiromitsu Morita, Motohiro Nishida, Akira Honda, Yushi Ito

From the Department of Physiology (R.I., A.H.), Fukuoka University School of Medicine, Japan; Department of Pharmacology (L.J.J., J.S., H.M., Y.I.), Graduate School of Medical Sciences; and Department of Pharmacology and Toxicology (M.N.), Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; and Department of Anatomy and K.K. Leung Brain Research Centre (J.S.), the Fourth Military Medical University, Xi’an, China.

Correspondence to Ryuji Inoue, MD, PhD, Department of Physiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan. E-mail inouery{at}fukuoka-u.ac.jp

This Review is part of a thematic series on TRP Channels in the Cardiovascular System, which includes the following articles:

Recent Developments in Vascular Endothelial Cell TRP Channels

Transient Receptor Potential Channels in Cardiovascular Function and Disease
Bernd Nilius Guest Editor

Sustained elevation in the intracellular Ca²⁺ concentration via Ca²⁺ influx, which is activated by a variety of mechanisms, plays a central regulatory role for cardiovascular functions. Recent molecular biological research has disclosed an unexpectedly diverse array of Ca²⁺-entry channel molecules involved in this Ca²⁺ influx. These include more than ten transient receptor potential (TRP) superfamily members such as TRPC1, TRPC3–6, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, and polycystin (TRPP2). Most of them appear to be multimodally activated or modulated and show relevant features to both acute hemodynamic control and long-term remodeling of the cardiovascular system, and many of them have been found to respond not only to receptor stimulation but also to various forms of stimuli. There is good evidence to implicate TRPC1 in neointimal hyperplasia after vascular injury via store-depletion–operated Ca²⁺ entry. TRPC6 likely contributes to receptor-operated and mechanosensitive Ca²⁺ mobilizations, being involved in vasoconstrictor and myogenic responses and pulmonary arterial proliferation and its associated disease (idiopathic pulmonary arterial hypertension). Considerable evidence has also been accumulated for unique involvement of TRPV1 in blood flow/pressure regulation via sensory vasoactive neuropeptide release. New lines of evidence suggest that TRPV2 may act as a Ca²⁺-overloading pathway associated with dystrophic cardiomyopathy, TRPV4 as a mediator of endothelium-dependent hyperpolarization, TRPM7 as a proproliferative vascular Mg²⁺ entry channel, and TRPP2 as a Ca²⁺-entry channel requisite for vascular integrity. This review attempts to provide an overview of the current knowledge on TRP proteins and discuss their possible roles in cardiovascular functions and diseases.

Key Words: cardiovascular function • non–voltage-gated Ca²⁺-entry channel • transient receptor potential protein • receptor stimulation • growth factor • mechanotransduction • cardiovascular remodeling

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