Piezo buffers mechanical stress via modulation of intracellular Ca2+ handling in the Drosophila heart

Abstract

Throughout its lifetime the heart is buffeted continuously by dynamic mechanical forces resulting from contraction of the heart muscle itself and fluctuations in haemodynamic load and pressure. These forces are in flux on a beat-by-beat basis, resulting from changes in posture, physical activity or emotional state, and over longer timescales due to altered physiology (e.g. pregnancy) or as a consequence of ageing or disease (e.g. hypertension). It has been known for over a century of the heart’s ability to sense differences in haemodynamic load and adjust contractile force accordingly (Frank, Z. biology, 1895, 32, 370–447; Anrep, J. Physiol., 1912, 45 (5), 307–317; Patterson and Starling, J. Physiol., 1914, 48 (5), 357–79; Starling, The law of the heart (Linacre Lecture, given at Cambridge, 1915), 1918). These adaptive behaviours are important for cardiovascular homeostasis, but the mechanism(s) underpinning them are incompletely understood. Here we present evidence that the mechanically-activated ion channel, Piezo, is an important component of the Drosophila heart’s ability to adapt to mechanical force. We find Piezo is a sarcoplasmic reticulum (SR)-resident channel and is part of a mechanism that regulates Ca2+ handling in cardiomyocytes in response to mechanical stress. Our data support a simple model in which Drosophila Piezo transduces mechanical force such as stretch into a Ca2+ signal, originating from the SR, that modulates cardiomyocyte contraction. We show that Piezo mutant hearts fail to buffer mechanical stress, have altered Ca2+ handling, become prone to arrhythmias and undergo pathological remodelling.

Mechanisms Controlling Hemolymph Circulation Under Resting Conditions In The Chagas Disease VectorRhodnius Prolixus(Stål)

“…Piezo proteins are a recently characterized family of proteins associated to cell membrane. They are sensitive to mechanical forces, facilitating the influx of cations (Coste et al, 2010, 2012) including Ca 2+ (Zechini et al, 2022) and they were associated to multiple functions (see Wu et al, 2017). Originally characterized in vertebrates, they were also found in invertebrates.…”

“…Originally characterized in vertebrates, they were also found in invertebrates. In D. melanogaster , these proteins proved to be involved, in nociception (Kim et al, 2012), control of meal size (Min et al, 2021) and cardiomyocytes activity (Zechini et al, 2022).…”

“…melanogaster, these proteins proved to be involved, in nociception (Kim et al, 2012), control of meal size (Min et al, 2021) and cardiomyocytes activity (Zechini et al, 2022).…”

“…They are also present in Drosophila melanogaster (Kim et al, 2012). Indeed, in D. melanogaster , it has been shown that piezo-like proteins would modulate intracellular Ca 2+ concentration in the heart (Zechini et al, 2022). Based on experimental designs involving Piezo protein agonists (Jedi 1 and Jedi 2) we found that both, DV contractions, as well as the peristaltic movements of the crop depend also on piezo-like proteins.…”

Conserved Chamber-Specific Polyploidy Maintains Heart Function inDrosophila

“…Drosophila melanogaster offers a highly tractable system to uncover conserved developmental regulation and functions of cardiomyocyte biology (Martínez-Morentin et al, 2015; Saha et al, 2022; Wessells et al, 2004; Wolf et al, 2006; Yu et al, 2013; Yu et al, 2015; Zechini et al, 2022). Flies and mammals share evolutionally conserved transcription factors that specify cardiac cell fate (Olson, 2006).…”