Block of postjunctional muscle-type acetylcholine receptors in vivo causes train-of-four fade in mice.

Nagashima, M; Sasakawa, T; Schaller, S J; Martyn, J A J

doi:10.1093/bja/aev037

2015

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Title:: Block of postjunctional muscle-type acetylcholine receptors in vivo causes train-of-four fade in mice.
Document type:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Article
Author(s):: Nagashima, M; Sasakawa, T; Schaller, S J; Martyn, J A J
Abstract:: Train-of-four (TOF) fade during nerve-mediated muscle contraction is postulated to be attributable to inhibition of prejunctional nicotinic ?3?2 acetylcholine receptors (nAChRs), while decrease of twitch tension is attributable to block of postjunctional muscle nAChRs. The validity of these presumptions was tested using specific prejunctional and postjunctional nAChR antagonists, testing the hypothesis that fade is not always a prejunctional phenomenon.Pentobarbital anaesthetized mice had TOF fade measured after administration of: either 0.9% saline; the prejunctional ?3?2 nAChR antagonist, dihydro-?-erythroidine (DH?E); the postjunctional nAChR antagonists, ?-bungarotoxin (?-BTX) or ?-conotoxin GI; and a combination of ?-BTX and DH?E; or a combination of ?-conotoxin GI and DH?E.Saline caused no neuromuscular changes. Administration of muscle nAChR antagonists, ?-BTX or ?-conotoxin GI caused significant decrease of twitch tension and TOF fade compared with baseline (P<0.01). DH?E alone caused no change of twitch tension or fade even after 90 min, but its coadministration with ?-BTX or ?-conotoxin GI significantly accelerated the onset of paralysis and degree of fade compared with ?-BTX or ?-conotoxin GI alone (P<0.01).Occupation of postjunctional nAChRs alone by ?-BTX or ?-conotoxin GI causes fade. As the prejunctional effects of DH?E on fade became manifest only when co-administered with ?-BTX or ?-conotoxin GI, specific inhibition of prejunctional nAChR alone is not necessary and sufficient to cause fade. Fade observed during repetitive nerve stimulation can be because of block of either postjunctional nAChRs alone, or block of prejunctional and postjunctional nAChRs together.
Journal title abbreviation:: Br J Anaesth
Year:: 2015
Journal volume:: 115
Journal issue:: 1
Pages contribution:: 122-7
Language:: eng
Fulltext / DOI:: doi:10.1093/bja/aev037
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/25835024
Print-ISSN:: 0007-0912
TUM Institution:: Klinik für Anästhesiologie (DHM)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik für Anästhesiologie und Intensivmedizin (Prof. Schneider)Klinik für Anästhesiologie (DHM)2015