Rapidly adapting mechanically activated channels (RA) are expressed in primary afferent neurons and identified as Piezo2 ion channels. We made whole-cell voltage-clamp recordings from cultured dorsal root ganglion (DRG) neurons to study RA channel regulation. RA currents showed gradual increases in current amplitude (current "run-up") after establishing whole-cell mode when 0.33 mM GTP or 0.33 mM GTPγS was included in the patch pipette internal solution. RA current run-up was also observed in HEK293 cells that heterologously expressed Piezo2 ion channels. No significant RA current run-up was observed in DRG neurons when GTP was omitted from the patch pipette internal solution, when GTP was replaced with 0.33 mM GDP, or when recordings were made under the perforated patch-clamp recording configuration. Our findings revealed a GTP-dependent up-regulation of the function of piezo2 ion channels in DRG neurons. © 2013 Jia et al.; licensee BioMed Central Ltd.