Low-Intensity Ultrasound Modulates Ca2+ Dynamics in Human Mesenchymal Stem Cells via Connexin 43 Hemichannel

In recent years, ultrasound has gained attention innew biological applications due to its ability to inducespecific biological responses at the cellular level. Althoughthe biophysical mechanisms underlying the interactionbetween ultrasound and cells are not fully understood, manyagree on a pivotal role of Ca2+ signaling through mechanotransductionpathways. Because Ca2+ regulates a vastrange of downstream cellular processes, a better understandingof how ultrasound influences Ca2+ signaling could leadto new applications for ultrasound. In this study, weinvestigated the mechanism of ultrasound-induced Ca2+mobilization in human mesenchymal stem cells using47 MHz focused ultrasound to stimulate single cells at lowintensities (~ 110 mW/cm2). We found that ultrasound exposuretriggers opening of connexin 43 hemichannels on theplasma membrane, causing release of ATP into the extracellularspace. That ATP then binds to G-protein-coupled P2Y1purinergic receptors on the membrane, in turn activatingphospholipase C, which evokes production of inositoltrisphosphate and release of Ca2+ from intracellular store