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Cellular mechanisms of atracurium-induced tetanic fade in the isolated rat muscle.

Abstract：

:Although atracurium is a widely used neuromuscular blocker, we still lack knowledge regarding some of its cellular mechanisms of action. Thus, similar to other clinically used blockers atracurium induces, both in vivo and in vitro, fade of the tetanic contraction. However, the cellular mechanisms underlying this tetanic fade have never been systematically studied. In the present work these mechanisms were investigated in vitro. A sciatic nerve extensor digitorum longus muscle preparation of the rat was used. A combination of myographical and electrophysiological techniques was employed. Indirect twitches were evoked at 0.1 Hz and tetanic contractions at 50 Hz. Trains of end-plate potentials were evoked at a frequency of 50 Hz. The electrophysiological variables used in the analysis of the trains of end-plate potentials were: peak amplitude of the first end-plate potential in the train, peak amplitude of plateau end-plate potentials in the train, tetanic run-down of the end-plate potentials' train, quantal content of first and plateau end-plate potentials in the train, quantal size. In the myographical study atracurium, at a concentration of 2.4 microM, induced a complete fade of the tetanic contraction while only slightly affected the twitch. In the electrophysiological study atracurium, at the same 2.4 microM concentration, significantly decreased the amplitude of both first end-plate potentials in the train (control: 14.4 mV; atracurium: 3.2 mV) and plateau end-plate potentials (control: 10.8 mV; atracurium: 2.4 mV) and reinforced the tetanic run-down of the train of end-plate potentials, evaluated as the percent loss in amplitude of plateau end-plate potentials compared to first end-plate potentials in the trains (control: 25.2%; atracurium: 33.2%). Atracurium also significantly decreased the quantal content of first end-plate potentials in the train (control: 231; atracurium: 68), the quantal content of plateau end-plate potentials (control: 159; atracurium: 42) and the quantal size (control: 0.119 mV; atracurium: 0.075 mV). In relative terms the decrease in quantal content was about twice as large as the decrease in quantal size. This indicates that the fade of the tetanic contraction induced by atracurium (2.4 microM) is due to both pre- and postsynaptic blocking effects, the presynaptic one being stronger.

journal_name

Basic Clin Pharmacol Toxicol

journal_title

Basic & clinical pharmacology & toxicology

authors

Nascimento DC,Serra CS,Oliveira AC

doi

10.1111/j.1742-7843.2004.pto950103.x

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

9-14

issue

eissn

1742-7835

issn

1742-7843

pii

PTOpto950103

journal_volume

pub_type

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Cellular mechanisms of atracurium-induced tetanic fade in the isolated rat muscle.