Low-Intensity Ultrasound Modulates Ca<sup>2+</sup> Dynamics in Human Mesenchymal Stem Cells via Connexin 43 Hemichannel.

Author: Yoon CW1, Jung H1, Goo K1, Moon S1, Koo KM1, Lee NS1, Weitz AC1,2, Shung KK3
Affiliation: <sup>1</sup>Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. <sup>2</sup>Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, USA. <sup>3</sup>Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. kkshung@usc.edu.
Conference/Journal: Ann Biomed Eng.
Date published: 2018 Jan
Other: Volume ID: 46 , Issue ID: 1 , Pages: 48-59 , Special Notes: doi: 10.1007/s10439-017-1949-7. Epub 2017 Oct 30. , Word Count: 172

In recent years, ultrasound has gained attention in new biological applications due to its ability to induce specific biological responses at the cellular level. Although the biophysical mechanisms underlying the interaction between ultrasound and cells are not fully understood, many agree on a pivotal role of Ca2+ signaling through mechanotransduction pathways. Because Ca2+ regulates a vast range of downstream cellular processes, a better understanding of how ultrasound influences Ca2+ signaling could lead to new applications for ultrasound. In this study, we investigated the mechanism of ultrasound-induced Ca2+ mobilization in human mesenchymal stem cells using 47 MHz focused ultrasound to stimulate single cells at low intensities (~ 110 mW/cm2). We found that ultrasound exposure triggers opening of connexin 43 hemichannels on the plasma membrane, causing release of ATP into the extracellular space. That ATP then binds to G-protein-coupled P2Y1 purinergic receptors on the membrane, in turn activating phospholipase C, which evokes production of inositol trisphosphate and release of Ca2+ from intracellular stores.

KEYWORDS: ATP; Calcium signaling; Mechanotransduction; Purinergic signaling

PMID: 29086222 DOI: 10.1007/s10439-017-1949-7