Piezo1 stretch-activated channel activity differs between bone marrow-derived and cardiac tissue-resident macrophages

Abstract

AbstractMacrophages (MΦ) play pivotal roles in tissue homeostasis and repair. Their mechanical environment recently emerged as a key modulator of various cell functions, and MΦ mechanosensitivity is likely to be critical for cellular activity in particular in a rhythmically contracting organ such as the heart. MΦ,in-vitro-differentiated from bone marrow (MΦBM), form a popular cell model for research. This study explores the activity of stretch-activated ion channels (SAC) in murine MΦBMand compares it to SAC activity in cardiac tissue-resident MΦ (MΦTR). Our main findings are: i) MΦBMand MΦTRhave stretch-induced currents, indicating expression of functional SAC at their plasma membrane; ii) the current profiles in MΦBMand in MΦTRshow characteristics of cation non-selective SAC; iii) unlike in MΦBM, Piezo1 ion channel activity at the plasma membrane of MΦTRis not detectable, neither by assessing electrophysiological activity using the patch clamp technique, nor by measuring cytosolic calcium concentration upon perfusion with Yoda1, a Piezo1 channel agonist. In mature scars after ventricular cryoablation, stretch-induced current characteristics of MΦTRare not significantly different compared to non-injured control tissue, even though scars are expected to contain a mix of pre-existing and circulation-recruited MΦ. This suggests that MΦ invading injured cardiac tissue either phenoconvert their mechanosensitivity from MΦBMto MΦTR, or that thein vitrodifferentiation protocols used to obtain MΦBMgenerate cells that differ from MΦ recruited from the circulation during tissue repairin vivo. Further investigations will explore SAC identity in lineage-traced MΦ in scar tissue, and compare mechanosensitivity of circulating monocytes with that of MΦBM.Key pointsMΦBMand MΦTRhave stretch-induced currents, indicating expression of functional SAC at their plasma membrane;The current profiles in MΦBMand in MΦTRshow characteristics of cation non-selective SAC;Unlike in MΦBM, Piezo1 ion channel activity at the plasma membrane of MΦTRis not detectable