Low-intensity ultrasound activates transmembrane chloride flow through CFTR

Ultrasound has been demonstrated to activate mechanosensitive channels, which is considered the main mechanism of ultrasound neuromodulation. Currently, all channels that have been shown to be sensitive to ultrasound are cation channels. In addition to cation channels, anion channels also play indispensable roles in neural function. However, there have been no research on ultrasound regulation of anion channels until now. If anion channels can be activated by ultrasound as well, they will inevitably lead to more versatility in ultrasound neuromodulation. Cystic fibrosis transmembrane transduction regulator (CFTR) has been demonstrated to be a mechanically sensitive channel, mediating anionic transmembrane flow. To identify that CFTR is sensitive to ultrasound, CFTR was exogenously expressed in HEK293T cells and was stimulated by low intensity ultrasound. Outward currents in CFTR-expressed HEK293T cells were observed by using whole-cell patch clamp when ultrasound (0.8 MHz, 0.20 MPa) was delivered to these cells. These currents were abolished when the CFTR inhibitor (GlyH101) was applied to the solution or chloride ions was cleared from the solution. Meanwhile, the amplitude of these currents increased when the CFTR agonist (Forskolin) was applied. These results suggest that ultrasound stimuli can activate the CFTR to mediate transmembrane flowing of chloride ions at the single cell level. These findings may expand the application of ultrasound in the neuromodulation field.