Effect of Anesthetics on Acetylcholine Release from the Myoneural Junction 1

Abstract

It has been reported that diethyl ether as well as other intravenous and inhalation anesthetics have varying depressant actions on neuromuscular transmission (1-3). With respect to diethyl ether this has been ascribed to a curare like action on the postjuctional membrane (4, 5). However, in recent years curare as well as other competitive neuromuscular blocking agents have been shown to have depressant action on the motor nerve terminal resulting in reduction of acetylcholine output (6, 7).

This work was conducted to elucidate the effects of some intravenous and inhalation anesthetics on acetylcholine output and thus gain a direct measure of activity on the nerve terminal. If they have a nerve terminal action, then they should reduce the amount of acetylcholine released upon nerve stimulation.

Methods. Frog sciatic nerve gastrocnemius muscle preparation. Frogs weighing between 20 and 25 g of the species Rana pipiens were stunned and decapitated. The skin was removed exposing the gastrocnemius muscle. The sciatic nerve was dissected free, ligated and cut. The gastrocnemius muscle was freed from the surrounding tissue and removed along with the sciatic nerve. The origin of the muscle was connected to a stationary metal rod while its tendon was attached to a transducer. The muscle was then placed in a 15 ml bath containing eserinized frog Ringer's solution (NaCl, 111.23; KCl, 1.88; NaH₂PO₄, 0.04; glucose, 11.10; NaHCO₃, 4.76; CaCl₂, 0.82; physostigmine 0.31 mmoles/liter) and bubbled with 100% O₂. The intravenous anesthetics were added directly to the bath. The inhalation agents were vaporized in a copper kettle and delivered to the bath mixed with 100% O₂. Interrupted supramaximal tetanic stimulation was applied to the nerve for 0.2 sec every 10 sec. The stimulation parameters were a frequency of 250 Hz, 1 msec duration and 5 V.