Enhancement of ASIC currents by angiotensin II in rat dorsal root ganglion neurons.

Emerging findings indicate that angiotensin II (Ang II) and its receptors, namely type 1 (AT1R) and type 2 (AT2R), are expressed in dorsal root ganglion (DRG) and involved in the nociception of sensory neurons. However, the mechanisms remain unknown. The purpose of this investigation is to determine the role of Ang II in the regulation of ion channels in nociceptive DRG neurons. Herein, we found that the application of Ang II for 10 min enhanced the electrophysiological activity of acid-sensing ion channels (ASICs) in rat DRG neurons. Ang II increased acid-evoked ASIC currents in a concentration-dependent manner. Ang II increased the maximum response of ASICs to acidic stimuli without changing their sensitivity. Ang II enhanced ASIC currents through AT1R but not AT2R. The enhancing effect of Ang II on ASIC currents was prevented by either the PKC inhibitor GF109203x, or the ERK inhibitor U0126, but not by the p38 inhibitor SB202190 or the JNK inhibitor SP600125. Moreover, Ang II increased the action potentials triggered by acidic stimuli. Finally, intraplantar injection of Ang II dose-dependently exacerbated acid-induced nociceptive behavior in rats through local AT1R. These results indicated that Ang II enhanced the functional activity of ASICs through a mechanism that depended on AT1R, the intracellular PKC, and the ERK signaling pathway. Our findings provided evidence that Ang II is a promising target for developing new treatments for pain, at least for pain associated with tissue acidification.