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

Abstract Macrophages (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 (MΦ BM ), form a popular cell model for research. This study explores the activity of stretch-activated ion channels (SAC) in murine MΦ BM and compares it to SAC activity in cardiac tissue-resident MΦ (MΦ TR ). Our main findings are: i) MΦ BM and MΦ TR have stretch-induced currents, indicating expression of functional SAC at their plasma membrane; ii) the current profiles in MΦ BM and in MΦ TR show characteristics of cation non-selective SAC; iii) unlike in MΦ BM , Piezo1 ion channel activity at the plasma membrane of MΦ TR is 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 MΦ TR are 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 MΦ BM to MΦ TR , or that the in vitro differentiation protocols used to obtain MΦ BM generate cells that differ from MΦ recruited from the circulation during tissue repair in vivo . Further investigations will explore SAC identity in lineage-traced MΦ in scar tissue, and compare mechanosensitivity of circulating monocytes with that of MΦ BM . Key points MΦ BM and MΦ TR have stretch-induced currents, indicating expression of functional SAC at their plasma membrane; The current profiles in MΦ BM and in MΦ TR show characteristics of cation non-selective SAC; Unlike in MΦ BM , Piezo1 ion channel activity at the plasma membrane of MΦ TR is not detectable