title: Competitive inhibition of the nondepolarizing muscle relaxant rocuronium on nicotinic acetylcholine receptor channels in the rat superior cervical ganglia.
abstract: A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.
authors.affiliation: *Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; †Department of Anesthesiology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China; and ‡Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chengmi
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhenmeng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhang
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
authors.forename: Yuming
authors.initials: Y
authors.lastname: Sun
authors.forename: Liqun
authors.initials: L
authors.lastname: Yang
authors.forename: Feixiang
authors.initials: F
authors.lastname: Wu
authors.forename: Jijian
authors.initials: J
authors.lastname: Zheng
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D000077123:Rocuronium; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014665:Vasodilator Agents; D000109:Acetylcholine; D000077123:Rocuronium