Channelling the Force to Reprogram the Matrix: Mechanosensitive Ion Channels in Cardiac Fibroblasts

Abstract

Cardiac fibroblasts (CF) play a pivotal role in preserving myocardial function and integrity of the heart tissue after injury, but also contribute to future susceptibility to heart failure. CF sense changes to the cardiac environment through chemical and mechanical cues that trigger changes in cellular function. In recent years, mechanosensitive ion channels have been implicated as key modulators of a range of CF functions that are important to fibrotic cardiac remodelling, including cell proliferation, myofibroblast differentiation, extracellular matrix turnover and paracrine signalling. To date, seven mechanosensitive ion channels are known to be functional in CF: the cation non-selective channels TRPC6, TRPM7, TRPV1, TRPV4 and Piezo1, and the potassium-selective channels TREK-1 and KATP. This review will outline current knowledge of these mechanosensitive ion channels in CF, discuss evidence of the mechanosensitivity of each channel, and detail the role that each channel plays in cardiac remodelling. By better understanding the role of mechanosensitive ion channels in CF, it is hoped that therapies may be developed for reducing pathological cardiac remodelling.

Keywords

• ion channels
• mechanical signalling
• mechanosensation
• cardiac fibroblasts
• cardiac remodelling
• extracellular matrix