Inhibition of mobilization of acetylcholine: the weak link in neuromuscular transmission during partial neuromuscular block with d-tubocurarine.
The authors have demonstrated earlier, by direct measurement of acetylcholine (ACh), that d-tubocurarine (d-Tc) and other nondepolarizing muscle relaxants decrease the release of ACh from the indirectly stimulated mouse hemidiaphragm preparation. It was the purpose of the present study to determine whether the decrease of the stimulated release of ACh and the increase in the intensity of the partial neuromuscular block observed at higher stimulation rates is caused by the inhibition of mobilization of ACh from reserve depots to release sites or by inhibition of the release process itself. To attain our objective, the authors have investigated the influence of the progressive increase of the rate of stimulation from 0.1 to 1, 2, 3, and 5 Hz on the force of contraction on the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation in the absence of drugs and after about 20% neuromuscular block produced by d-Tc or by Mg2+. The latter is known to inhibit the Ca2+ dependent release of ACh. In the absence of drugs increasing the stimulation rate increased the force of contraction, in vivo and in vitro, during both indirect and direct stimulation. In the phrenic nerve-hemidiaphragm preparation the increase was significant at 1, 2, 3, and 5 Hz (P less than 0.001) with both types of stimulation. In the sciatic nerve-tibialis anterior preparation the force of contraction was only higher at 3 and 5 Hz (P less than 0.01). The similar magnitude of the increase of the force of contraction during direct and indirect stimulation indicates that it is caused by facilitation of the contraction of the muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Foldes
F F
FF
Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Chaudhry
I A
IA
Kinjo
M
M
Nagashima
H
H
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003964:Diaphragm / Q000294:innervation; D004558:Electric Stimulation; D008297:Male; D009132:Muscles / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve; D009435:Synaptic Transmission / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000378:metabolism; D013977:Tibia; D014403:Tubocurarine / Q000494:pharmacology*
D000109:Acetylcholine; D014403:Tubocurarine