Free
Correspondence  |   June 2007
Role of Presynaptic Acetylcholine Autoreceptors at Motor Nerve Endings on Tetanic and Train-of-four Fade Seen during a Nondepolarizing Neuromuscular Block
Author Affiliations & Notes
  • Zhijun Lu, M.D.
    *
  • *Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Article Information
Correspondence
Correspondence   |   June 2007
Role of Presynaptic Acetylcholine Autoreceptors at Motor Nerve Endings on Tetanic and Train-of-four Fade Seen during a Nondepolarizing Neuromuscular Block
Anesthesiology 6 2007, Vol.106, 1243. doi:10.1097/01.anes.0000265457.47797.4c
Anesthesiology 6 2007, Vol.106, 1243. doi:10.1097/01.anes.0000265457.47797.4c
To the Editor:—
We read with interest article by Jonsson et al.  1 suggesting that nondepolarizing neuromuscular blocking agents concentration-dependently inhibit human neuronal acetylcholine autoreceptors (nAChRs). The authors argue that the inhibition of the presynaptic α3β2nAChR subtype plays an important role in tetanic and train-of-four fade seen during nondepolarizing neuromuscular blockade.1 However, there is evidence from previous studies that are not consistent with this explanation. For example, α-conotoxin MII, a highly selective antagonist for α3β2-containing nAChRs, does not result in tetanic fade, although acetylcholine release was decreased. This may be related to the high safety margin of neuromuscular transmission. If the fluid bathing the synapse is changed to one with a high concentration of magnesium, which reduces the release of acetylcholine, α-conotoxin MII significantly decreases the tetanic ratio.2 These results suggested that, only under conditions of decreased safety margin, blockade of presynaptic α3β2nAChRs could induce tetanic and train-of-four fade.
Nondepolarizing neuromuscular blocking agents might influence synaptic safety margins in two ways. First, most nondepolarizing neuromuscular blocking agents used currently are nonselective antagonists for both presynaptic and postsynaptic nAChRs, and postsynaptic nAChRs are clearly one of the most important factors involved in transmission safety. Second, recent studies have found that release of acetylcholine was mediated by some metabotrophic receptors, which coexisted with nicotinic receptors at nerve endings. For example, purinergic P2Y,3 adenosine A1,4 and muscarinic M1receptors5 were related to inhibition of acetylcholine release at rat neuromuscular junction. At least up to now, we cannot exclude the possibility that nondepolarizing neuromuscular blocking agents would impact acetylcholine release through these receptors.
In summary, we think that during nondepolarizing neuromuscular blockade, tetanic and train-of-four fade cannot be explained simply by blockade of presynaptic α3β2nAChRs; other unknown factors may be involved.
*Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
References
Jonsson M, Gurley D, Dabrowski M, Larsson O, Johnson EC, Erriksson LI: Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors. Anesthesiology 2006; 105:521–33Jonsson, M Gurley, D Dabrowski, M Larsson, O Johnson, EC Erriksson, LI
Faria M, Oliveira L, Timóteo MA, Lobo MG, Correia-De-Se P: Blockade of neuronal facilitatory nicotinic receptors containing subunits contribute to tetanic fade in the rat isolated diaphragm. Synapse 2003; 49:77–88Faria, M Oliveira, L Timóteo, MA Lobo, MG Correia-De-Se, P
Lorenzo SD, Veggetti M, Muchnik S, Losavio A: Presynaptic inhibition of spontaneous acetylcholine release mediated by P2Y receptors at the mouse neuromuscular junction. Neuroscience 2006; 142:71–85Lorenzo, SD Veggetti, M Muchnik, S Losavio, A
Lorenzo SD, Veggetti M, Muchnic S, Losavio A: Presynaptic inhibition of spontaneous acetylcholine release induced by adenosine at mouse neuromuscular junction. Br J Pharmacol 2004; 142:113–24Lorenzo, SD Veggetti, M Muchnic, S Losavio, A
Santafé MM, Salon I, Garcia N, Lanuza MA, Uchitel OD, Tomàs J: Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat. Eur J Neurosci 2003; 17:119–27Santafé, MM Salon, I Garcia, N Lanuza, MA Uchitel, OD Tomàs, J