TRPC Channels in Cardiac Plasticity.

Takuro Numaga-Tomita,Motohiro Nishida

doi:10.3390/cells9020454

Abstract

The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology. Roles of TRPC channels in cardiac physiology have been reported in pathological cardiac remodeling. In this review, we summarize recent findings regarding the importance of TRPC channels in flexible cardiac remodeling (i.e., cardiac plasticity) in response to environmental stresses and discuss questions that should be addressed in the near future.

Highlights

The heart is a pump, delivering oxygen and nutrients to all tissues in the body through blood vessels.During development, heart size and contractile force gradually increase, which is accompanied by structural changes, e.g., hypertrophy, T-tubule formation, and arrangement of sarcomeres [1]
We reported that TRPC6 functions as a negative regulator of TRPC3 coupling to NADPH oxidase 2 (Nox2) through a competitive interaction [37]
CaN/NFAT pathway cannot explain all mechanisms of cardiac hypertrophy induced by excessive environmental stresses on cardiomyocytes

Summary

Introduction

The heart is a pump, delivering oxygen and nutrients to all tissues in the body through blood vessels. TRPC proteins have two important roles: one as a functional channel activated by mechanical stretch or endoplasmic reticulum store depletion and the other as a platform to organize receptor-activated. As a result of their universal activation mechanism in many cell types, TRPC channels play important roles in basic cellular responses including proliferation, differentiation, and death in response to various environmental stimuli. Recent findings indicate that in addition to PLC-mediated activation, TRPC channels are multimodally activated by environmental stimuli such as mechanical stretch, hypoxia, and oxidative stress [14,15,16,17,18,19]. The actual mechanism of TRPC channel downstream surface receptor activation is still not completely understood [34], its importance in cardiac plasticity has been extensively documented in the model of neurohumoral-factor-induced cardiac remodeling. We review recent findings about TRPC channels in cardiac remodeling and raise models and questions that need to be addressed in the near future

Functional TRPC Channel Expression and Interaction with Other Proteins

Cardiac Hypertrophy

Cardiac Atrophy

Cardiac Fibrosis

Conclusions