PRESYNAPTIC AND POSTSYNAPTIC MECHANISMS INVOLVED IN TETANIC FADE INDUCED BY PANCURONIUM IN THE ISOLATED RAT MUSCLE

The mechanisms underlying the fade of the tetanic contraction induced by pancuronium were studied in vitro by means of myographical and elec trophysiological techniques in the extensor digitorum longus muscle of the rat. Pancuronium (0.5 mu mol/l) induced a complete fade of the te tanic contraction while leaving the twitch unaffected. At the same con centration it decreased the amplitude and increased the tetanic rundow n of trains of endplate potentials (e.p.ps) evoked in the frequency of 50 Hz. The electrophysiological changes induced by pancuronium were d ue to decreases in both quantal sizes and quantal contents of the e.p. ps. The former effect was the result of a postsynaptic competitive act ion and the latter of a presynaptic inhibitory action of that compound . The decrease in quantal. content affected the e.p.ps starting from t he first in the train and became larger during the generation of the s equence of e.p.ps. This intensified their tetanic rundown. It is concl uded that the fade of the tetanic contraction induced by pancuronium i s due to a summation of pre- and postsynaptic actions and, therefore, not only to an increase in the tetanic rundown of e.p.ps. Possible exp lanations for the distinct abilities of neuromuscular blockers in affe cting tetani and twitches in a differential manner are also discussed.