Pathophysiological Roles of the TRPV4 Channel in the Heart

Cells. 2023 Jun 17;12(12):1654. doi: 10.3390/cells12121654.

Abstract

The transient receptor potential vanilloid 4 (TRPV4) channel is a non-selective cation channel that is mostly permeable to calcium (Ca2+), which participates in intracellular Ca2+ handling in cardiac cells. It is widely expressed through the body and is activated by a large spectrum of physicochemical stimuli, conferring it a role in a variety of sensorial and physiological functions. Within the cardiovascular system, TRPV4 expression is reported in cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs), where it modulates mitochondrial activity, Ca2+ homeostasis, cardiomyocytes electrical activity and contractility, cardiac embryonic development and fibroblast proliferation, as well as vascular permeability, dilatation and constriction. On the other hand, TRPV4 channels participate in several cardiac pathological processes such as the development of cardiac fibrosis, hypertrophy, ischemia-reperfusion injuries, heart failure, myocardial infarction and arrhythmia. In this manuscript, we provide an overview of TRPV4 channel implications in cardiac physiology and discuss the potential of the TRPV4 channel as a therapeutic target against cardiovascular diseases.

Keywords: TRPV4 channels; TRPV4-KO mice; action potential; calcium homeostasis; endothelial cells; fibroblasts; heart; myocytes.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Myocardial Infarction* / metabolism
  • Myocytes, Cardiac / metabolism
  • Pregnancy
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels* / metabolism

Substances

  • Transient Receptor Potential Channels
  • TRPV Cation Channels
  • TRPV4 protein, human

Grants and funding

This work received financial support from the French Government as part of the “Investments of the Future” program managed by the National Research Agency (ANR-10-IAHU-04). SB and TD are supported by the French ANR CANALBRET (19-CE44-0010-02) and the New Aquitaine regional council PHYSTRIG (AAPR2020I-2019-8151810). Finally, DB is supported by the ANR MEGAVOLT (18CE14002701).