TMEM120A negatively regulates rapidly adapting mechanically activated currents in mouse DRG neurons. Mouse DRG neurons were transfected with Tmem120a-siRNA or nontargeting negative control siRNA (Sham-siRNA) as described in the Materials and methods section. Whole-cell patch-clamp experiments were performed at −60 mV with mechanically activated currents evoked by increasing indentation with a blunt glass probe. (A) DRG neurons with rapidly adapting (RA) inactivation kinetics indicative of native Piezo2 were measured. Current amplitudes are plotted (mean ± SEM) for Sham-siRNA neurons with RA kinetics (black) and for Tmem120a -siRNA neurons with RA kinetics (orange). (B) Representative RA-type current traces. (C and D) Scatter plots and mean ± SEM for current amplitudes at 6.8 and 12.0 μm indentations. (E) Scatter plots and mean ± SEM for mechanical threshold (blunt glass probe indentation depth required to elicit RA type currents). (F) Percentage of cells displaying RA, intermediate adapting (IA), and slow adapting (SA) currents and nonresponding neurons (NR) for those transfected with Sham-siRNA and Tmem120a -siRNA. The electrophysiology data are from four independent DRG neuron preparations and transfections, n = 54 for Sham-siRNA, and n = 52 for Tmem120a -siRNA. Statistical significance was assessed using the chi-squared test. (G) Representative RA, IA, and SA current traces. Statistical significance for C–E was calculated with the Mann-Whitney test.