Low-energy shock waves evoke intracellular Ca²⁺ increases independently of sonoporation

Low-energy shock waves (LESWs) accelerate the healing of a broad range of tissue injuries, including angiogenesis and bone fractures. In cells, LESW irradiations enhance gene expression and protein synthesis. One probable mechanism underlying the enhancements is mechanosensing. Shock waves also can induce sonoporation. Thus, sonoporation is another probable mechanism underlying the enhancements. It remains elusive whether LESWs require sonoporation to evoke cellular responses. An intracellular Ca²⁺ increase was evoked with LESW irradiations in endothelial cells. The minimum acoustic energy required for sufficient evocation was 1.7 μJ/mm². With the same acoustic energy, sonoporation, by which calcein and propidium iodide would become permeated, was not observed. It was found that intracellular Ca²⁺ increases evoked by LESW irradiations do not require sonoporation. In the intracellular Ca²⁺ increase, actin cytoskeletons and stretch-activated Ca²⁺ channels were involved; however, microtubules were not. In addition, with Ca²⁺ influx through the Ca²⁺ channels, the Ca²⁺ release through the PLC-IP₃-IP₃R cascade contributed to the intracellular Ca²⁺ increase. These results demonstrate that LESW irradiations can evoke cellular responses independently of sonoporation. Rather, LESW irradiations evoke cellular responses through mechanosensing.