Resistance to D-tubocurarine of the rat diaphragm as compared to a limb muscle: influence of quantal transmitter release and nicotinic acetylcholine receptors. - Archive ouverte HAL Access content directly
Journal Articles Anesthesiology Year : 2009

Resistance to D-tubocurarine of the rat diaphragm as compared to a limb muscle: influence of quantal transmitter release and nicotinic acetylcholine receptors.

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Abstract

BACKGROUND: The diaphragm is resistant to competitive neuromuscular blocking agents, as compared to peripheral muscles. The basis of this difference may be a higher concentration of acetylcholine released or higher number of postsynaptic nicotinic acetylcholine receptors in diaphragmatic neuromuscular junctions. METHODS: Nerve-evoked twitch-tension was measured in rat hemidiaphragm as was Extensor digitorum longus (EDL) nerve-muscle preparation to determine the effective D-tubocurarine concentration that decreased twitch responses by 50%. The mean quantal content of endplate potentials was determined in single junctions in a low-Ca(2+), high-Mg(2+) Krebs-Ringer medium. Strips of hemidiaphragm and EDL muscle, containing the endplate regions, were used to determine the number of nAChR nicotinic acetylcholine receptor binding sites with the aid of radiolabeled [(125)I]alpha-bungarotoxin. RESULTS: The effective D-tubocurarine concentration that decreased twitch responses by 50% (median [interquartile range]) was seven-fold higher in the hemidiaphragm than in the EDL (1.82 microm [1.43-2.20] vs. 0.26 microm [0.23-0.29], P < 0.01). The median of the mean quantal content was higher in the hemidiaphragm than in the EDL (0.57 [0.44-0.84] vs. (0.14 [0.11-0.19], P < 0.01). The number of specific [(125)I]alpha-bungarotoxin binding sites to junctional nicotinic acetylcholine receptors was higher in the diaphragm than in the EDL (1.15 fmol/mg [0.48-1.70] vs. 0.55 fmol/mg [0.23-0.70 ], P < 0.05). CONCLUSION: The current study indicates that the resistance of the diaphragm to neuromuscular blocking agents can be explained by both a higher mean quantal content of endplate potentials and a higher number of nicotinic acetylcholine receptor binding sites than in the peripheral EDL muscle.

Dates and versions

hal-00377886 , version 1 (23-04-2009)

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Tu Nguyen-Huu, Jordi Molgó, Denis Servent, Philippe Duvaldestin. Resistance to D-tubocurarine of the rat diaphragm as compared to a limb muscle: influence of quantal transmitter release and nicotinic acetylcholine receptors.. Anesthesiology, 2009, 110 (5), pp.1011-5. ⟨10.1097/ALN.0b013e31819faeaa⟩. ⟨hal-00377886⟩

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