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.

Alpha2-adrenoceptor-independent inhibition of acetylcholine receptor channel and sodium channel by dexmedetomidine in rat superior cervical ganglion neurons

“…Acute isolation of single-rat SCG neurons Freshly dissociated single neurons from rat SCG were prepared using the method described previously (Uki et al, 1999;Zhang et al, 2014). The experimental protocol was approved by the Animal Research Ethics Committee of the Jinshan Hospital affiliated to the Fudan University (Permit Number: 2013-033-01), and carried out in strict accordance with the Guidelines for the Care and Use of Laboratory Animals published by the US National Institutes of Health (National Institutes of Health Publication No.…”

Bilirubin Modulates Acetylcholine Receptors In Rat Superior Cervical Ganglionic Neurons In a Bidirectional Manner

“…Neonatal SD rats were terminally anesthetized with CO 2 and immediately decapitated. Neurons from rat SCG were freshly dissociated as described previously 39 40 . Briefly, both sides of SCG were acutely dissociated from SD rats aged 4–6 days, and each SCG was sliced into 2–4 sections in ice-cold well-oxygenated bathing solution using a razor blade.…”

Transient Complete Atrioventricular Block Resulted from Cardiac Anaphylaxis Caused by Sugammadex

“…Rocuronium has also been reported to have affinities for these muscarinic receptors, and its affinities are lower than those of pancuronium, such that binding does not occur in the range of concentrations achieved with clinical use [5]. Rocuronium has been reported to block nicotinic acetylcholine receptors at the superior cervical ganglia of rats [6], and it has thus been suggested that the effects of rocuronium on the autonomic nervous system cannot be assumed to be negligible. Therefore, when rocuronium disappears rapidly following the administration of sugammadex, it is no wonder that sympathetic or parasympathetic hyperactivity might occur as a reaction.…”