Rat Isolated Phrenic Nerve‐diaphragm Preparation for Pharmacological Study of Muscle Spindle Afferent Activity: Effect of Oxotremorine

Abstract

1 Muscle spindle afferent discharges exhibiting an approximately linear length-frequency relation could be recorded from the phrenic nerve in the isolated phrenic nerve-diaphragm preparation of the rat. 2 Muscle spindle afferent discharges could be identified by their characteristic 'spindle pause' during muscle contraction and by their response to succinylcholine. 3 Cholinergic influence on spontaneous and stretch-induced afferent discharges was indicated by the augmentation produced by physostigmine and acetylcholine. (+)-Tubocurarine, but not atropine, prevented this augmentation indicating the presence of curariform cholinoceptors in muscle spindles. 4 Acetylcholine did not appear to be involved in the genesis of spindle afferent discharges as incubation with hemicholinium-3 and (+)-tubocurarine failed to affect the rate of spontaneous and stretch-induced spindle discharges. 5 Oxotremorine markedly increased the rate of spontaneous and stretch-induced spindle afferent discharges and this effect was prevented in the presence of hemicholinium-3 and (+)-tubocurarine. 6 These results with oxotremorine are of interest in connection with the observation that muscle spindle afferents are hyperactive in Parkinsonian patients.

Acetylcholine receptors in the equatorial region of intrafusal muscle fibres modulate mouse muscle spindle sensitivity

“…Finally, we used single unit muscle spindle afferent recordings with a much higher sensitivity allowing us to detect small modulatory activities, which apparently have escaped detection in previous studies (Smith & Albuquerque, ; Ganguly et al . ; Akoev, ).…”

“…Then, 30 μM d-tubocurarine (T2379, Sigma-Aldrich Chemie GmbH), 1.25 μM α-bungarotoxin (B1601, Life Technologies, Carlsbad, CA, USA) or 30 μM hemicholinium-3 (HC-3; Sigma-Aldrich) was added to the oxygenated ACSF. At this concentration, α-bungarotoxin and tubocurarine completely inhibit neuromuscular transmission (Ganguly et al 1978;Chang et al 1989;Wenningmann & Dilger, 2001). For control measurements 100 μL ACSF was added instead of a drug.…”

“…At this concentration, α‐bungarotoxin and tubocurarine completely inhibit neuromuscular transmission (Ganguly et al . ; Chang et al . ; Wenningmann & Dilger, ).…”

N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), a tremorogen, on rat diaphragm.

“…We earlier reported involvement of the skeletomotor apparatus in oxotremorine induced tremor (2)(3)(4). Thus it was felt worthwhile to examine the influence of LON-954 on the skeletal myoneural system by employing innervated and denervated rat diaphragm preparations to determine the pre and post-synaptic effects, if any.…”

“…The question of whether or not LON-954 also affects the other peripheral and spinal sites of oxotremorine action, for example, the intrafusal myoneural apparatus (4,9) and the recurrent inhibition in the spinal cord (10), are currently being examined in order to identify the common sites that may be involved in tremorogenesis.…”