Blockade of neuronal facilitatory nicotinic receptors containing alpha 3 beta 2 subunits contribute to tetanic fade in the at isolated diaphragm

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Miguel Faria (Author) ICBAS; oliveira, l (Author) Other; Timoteo, MA (Author) Other; Lobo, MG (Author) ICBAS; Paulo Correia de Sá (Author) ICBAS

Journal

Title: Synapse

Vol. 49 No. 2

Pages: 77-88

ISSN: 0887-4476

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 54 Citations

Scopus - 59 Citations

Other information

Authenticus ID: P-000-FSS

DOI: 10.1002/syn.10211

Abstract (EN): Nicotinic receptor (nAChR) subtypes involved in pre- and postjunctional actions underlying tetanic fade were studied in rat phrenic-nerve hemidiaphragms. We investigated the ability of subtype-specific nAChR antagonists to depress nerve-evoked contractions and [H-3]-acetylcholine ([H-3]-ACh) release. Muscle tension was transiently increased during brief high frequency trains (50 Hz for 5 sec). The rank potency order of nAChR antagonists to reduce tetanic peak tension was a-bungarotoxin > d-tubocurarine > mecamylamine > hexamethonium. Reduction of maximal tetanic tension produced by dihydro-beta-erythroidine (0.03-10 muM), methyllycaconitine (0.003-3 muM), and alpha-conotoxin MII (0.001-0.3 muM) did not exceed 30%. Besides reduction of peak tension d-tubocurarine (0.1-0.7 muM), mecamylamine (0.1-300 muM), and hexamethonium. (30-3,000 muM) also caused tetanic fading. With alpha-conotoxin MII (0.001-0.3 muM) and dihydro-beta-erythroidine (0.03-10 muM), tetanic fade was evident only after decreasing the safety factor of neuromuscular transmission (with high magnesium ions, 6-7 mM). The antagonist rank potency order to reduce evoked (50 Hz for 5 sec) [3 H]-ACh release from motor nerve terminals was alpha-conotoxin MII (0.1 muM) > dihydro-beta-erythroidine (1 muM) similar to d-tubocurarine (1 muM) > mecamylamine (100 muM) > hexamethonium (1,000 muM). When applied in a concentration (0.3 muM) above that producing tetanic paralysis, a-bungarotoxin failed to affect [H-3]-ACh release. Data obtained suggest that postjunctional neuromuscular relaxants interact with alpha-bungarotoxin-sensitive nicotinic receptors containing alpha1-subunits, whereas blockade of neuronal alpha3beta2-containing receptors produce tetanic fade by breaking nicotinic autofacilitation of acetylcholine release. (C) 2003 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12