Abstract
Aim:
To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying potencies at ɛ-AChR and γ-AChR.
Methods:
Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing ɛ-AChR or γ-AChR were used. The effects of NDMRs on nAChR were explored using whole-cell patch clamp technique.
Results:
NDMRs vecuronium (VEC), atracurium (ATR) and rocuronium (ROC) produced reversible, dose-dependent inhibition on the currents induced by 30 μmol/L acetylcholine both in innervated and denervated skeletal muscle cells. Compared to those obtained in innervated skeletal muscle cells, denervation shifted the concentration-response curves rightward and significantly increased the 50% inhibitory concentration (IC50) values (VEC: from 11.2 to 39.2 nmol/L, P<0.01; ATR: from 24.4 to 129.0 nmol/L, P<0.01; ROC: from 37.9 to 101.4 nmol/L, P<0.01). In HEK293 cell expression system, ATR was less potent at γ-AChR than ɛ-AChR (IC50 values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC50 values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at γ-AChR than ɛ-AChR (IC50 values: 22.3 vs 33.5 nmol/L, P<0.05).
Conclusion:
Magnitude differences of resistance to different NDMRs caused by denervation are associated with distinct potencies of NDMRs at nAChR subtypes.
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Abbreviations
- NDMRs:
-
nondepolarizing muscle relaxants
- nAChR:
-
nicotinic acetylcholine receptor
- γ-AChR:
-
fetal-type nicotinic acetylcholine receptor
- ɛ-AChR:
-
adult-type nicotinic acetylcholine receptor
- IC50:
-
half-maximal response
- dTC:
-
d-tubocurarine
- HEK293:
-
human embryonic kidney 293
- FDB:
-
flexor digitorum brevis
- DMEM:
-
Dulbecco's modified Eagle's medium
- ACh:
-
Acetylcholine
- INN:
-
innervated
- DEN:
-
denervated
- VEC:
-
vecuronium
- ATRA:
-
atracurium
- ROC:
-
rocuronium.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (No 30571796).
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Wang, H., Yang, B., Xu, Yf. et al. Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle. Acta Pharmacol Sin 31, 399–404 (2010). https://doi.org/10.1038/aps.2010.26
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DOI: https://doi.org/10.1038/aps.2010.26
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