SPECIFICITY OF EXCITATION OF MUSCLE SPINDLE AFFERENTS BY CHOLINERGIC SUBSTANCES

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois

The effects of intraarterially administered succinylcholine (SCh), acetylcholine (ACh), nicotine, DMPP and muscarine on acutely denervated muscle spindle afferent nerves and endings were compared. In order to characterize the role of dose and fiber types, at least four doses of each substance on each of 23 or more individual muscle spindle afferent units of a variety of conduction velocities were determined.

SCh, nicotine, DMPP, and ACh produced excitation of all spindle afferents examined, whereas muscarine caused a transient or longlasting decrease in afferent discharge frequency.

The magnitude of the increase in discharge frequency produced by SCh, nicotine, and DMPP was a function of the conduction velocity of the fiber of the afferent unit: the greater the conduction velocity the greater the degree of excitation. The major differences among the units were the consequence of the higher slope of dose-response curve of the more rapidly conducting afferents. On the faster fibers (Group Ia) SCh and nicotine were of the same order of potency.

Extrafusal neuromuscular block was also assessed: SCh was approximately 120 times as potent as nicotine; ACh was even less potent than nicotine. Muscarine was without detectable influence on the muscle twitch.

It is concluded that the excitatory cholinergic agents (ACh, SCh, DMPP, nicotine) have different sites and/or mechanisms of action in causing stimulation of muscle spindle afferent activity.