title: Inhibition of acid-sensing ion channel currents by propofol in rat dorsal root ganglion neurons.
abstract: Acid-sensing ion channels (ASICs), part of the epithelial sodium channel/degenerin family, are activated by extracellular protons. The ASICs play a significant role in the acidosis-mediated perception of pain. The anaesthetic agent propofol also exerts antinociceptive effects, but the underlying mechanisms for this effect are not clear. We used whole-cell patch clamping to investigate the effect of propofol on proton-gated currents in: (i) rat dorsal root ganglion (DRG) neurons; and (ii) HEK293 cells transfected with either ASIC1a or ASIC3. Propofol inhibited the amplitude of proton-gated currents in DRG neurons, but did not change the sensitivity of ASICs to H(+). Notably, propofol altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. In addition, we demonstrated that propofol inhibited ASICs by directly binding with these channels in HEK293 cells. These results suggest that propofol inhibits proton-gated currents in DRG neurons and that inhibition of proton-gated currents explains, in part, the antinociceptive effects of propofol in primary afferent neurons.
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lei
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Guizhi
authors.initials: G
authors.lastname: Wang
authors.forename: Jianchun
authors.initials: J
authors.lastname: Fei
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jingya
authors.initials: J
authors.lastname: Yu
authors.forename: Jingui
authors.initials: J
authors.lastname: Yu
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology*; D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D006993:Hypnotics and Sedatives; D015742:Propofol
keywords: acid-sensing ion channels; dorsal root ganglion; nociperception; pain; propofol