Blockade of intrafusal neuromuscular junctions of cat muscle spindles with gallamine

Abstract

SUMMARYThis is a report on the resistance to block of the motor terminals on intrafusal fibres of cat soleus muscle spindles using the drug gallamine triethiodide (Flaxedil). To minimize diffusion barriers and to permit accurate measurements of time courses, rather slow rates of gallamine infusion were used (0-15 mg min-1). The main finding made was that after gallamine infusion, when extrafusal tension had dropped to half, all dynamic fusimotor effects and eight of twenty static effects had fallen to 40 % or less of their control value. The remaining static effects persisted at 60-80 % of their control value. Where fusimotor fibres were stimulated together with one or two skeletomotor fibres, the influence of the skeletomotor axons was significant only after spindle biasing had fallen to low levels. When gallamine infusion was stopped extrafusal tension returned to control levels within 20-75 min, depending on the length of the block, while fusimotor responses did not fully recover within the recording period of up to 150 min. The combination for some fusimotor responses of an early fall and a late recovery when compared with extrafusal tension, suggested a greater sensitivity of these endings to the drug. A comparison of spindle responses to the drug succinyl choline (SCh) and to fusimotor stimulation in the presence of gallamine showed that SCh responses were rapidly reduced by gallamine and had a long recovery time course, as were some fusimotor responses. From this it is argued that fusimotor effects with a high sensitivity to gallamine blockade were associated with nuclear bag fibre contractions and the more resistant effects with nuclear chain fibre contraction. It is generally believed that intrafusal neuromuscular junctions are more resistant to neuromuscular blockers than extrafusal junctions. The present experiments provide evidence to the contrary for some intrafusal junctions. Since muscle relaxants are often used in general anaesthesia it is interesting to speculate about the recovery of function of proprioceptive reflexes and of kinaesthesia during the immediate post-anaesthetic period, in view of the large difference in recovery time for transmission at intrafusal and extrafusal junctions.

Signals of motor command bias joint position sense in the presence of feedback from proprioceptors

“…The rocuronium infusion reduced force to an average of 3% MVC, while animal studies with gallamine showed that a fall in extrafusal tension by one-half was accompanied by block of all dynamic and about one-third of static fusimotor effects (47). Furthermore, in whole body experiments in which the effective local concentration of the blocking agent was much lower than with the local infusion used here, the illusory changes in position were in the opposite direction to the direction of attempted contraction (20).…”

The Proprioceptive Senses: Their Roles in Signaling Body Shape, Body Position and Movement, and Muscle Force

“…They proposed that this was due to a weakened spindle signal as a result of an intrafusal motor terminal blockade. It is known that when a muscle is deeply paralyzed, sufficient to block motor terminals on both extrafusal and intrafusal fibers, during the recovery period the extrafusal fibers unblock first, with recovery of intrafusal terminals being delayed (365,427). During recovery, in the face of rapidly rising muscle force, the persisting intrafusal paralysis weakens the coactivation of spindles, and the lower level of afferent discharge leads to a reduction in the sense of force.…”

What is the role of muscle receptors in proprioception?

“…The interpretation preferred by the investigators was that while all extrafusal fibers were blocked by the paralyzing agent, by virtue of their higher blocking threshold, some fusimotor neuromuscular junctions were still functioning. 40 As a result of the attempted contraction there was coactivation of fusimotor neu-rons, leading to an increase in spindle discharge, which was interpreted by the subject as the muscle lengthening. In supplementary experiments, total muscle paralysis abolished the illusion, consistent with an interpretation based on incomplete paralysis.…”