Studies on the trophic influence of nerve on skeletal muscle

SUMMARY1. Rat extensor digitorum longus (EDL) muscles were examined after colchicine treatment of the sciatic nerve. Colchicine was applied in one of two ways: (i) a single sub-epineural injection; (ii) a chronically implanted silicone cuff.2. After the sub-epineural injection, the entire membrane of muscle fibres became sensitive to iontophoretically applied acetylcholine and the muscle action potentials became resistant to tetrodotoxin. However, the majority of these fibres were found to be normally innervated.3. These effects were not restricted to the EDL muscle of the cQlchicine injected side but were also found in the EDL muscle of the contralateral side, indicating that the action of colchicine was systemic.4. In the treated sciatic nerve there was a partial block of axonal transport of 3H-labelled proteins, which correlated with a partial paralysis of the ipsilateral leg. However, axoplasmic transport was found to be normal in the contralateral sciatic nerve and the contralateral limb was not paralysed despite the supersensitivity of the investigated muscle on that side.5. When colchicine was applied with a silicone cuff, denervation-like changes were confined to the ipsilateral EDL muscle. However, impulse conduction block at the level of the cuff was usually observed.6. It is concluded that (i) colchicine can produce denervation-like changes in normally active muscle without blocking axoplasmic transport, through an action probably exerted directly on the muscle membrane, and (ii) that colchicine-cuff experiments failed to provide unambiguous evidence in support of the existence of neurotrophic influences on the muscle membrane.

contrasting

confidence: 35%

The production of denervation‐like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity.

Cangiano¹,

Fried²

1977

“…Recent evidence that chronic application of vinblastine or colchicine to a nerve (reported to block axoplasmic transport but not the conduction of action potentials) results in the development of extrajunctional sensitivity, makes it unlikely that activity is the sole determinant of the functional state of the mammalian muscle fibre membrane (Hofmann & Thesleff, 1972;Albuquerque, Warnick, Tasse & Sansone, 1972).…”

Section: Purves and B Sakmannmentioning

confidence: 99%

The effect of contractile activity on fibrillation and extrajunctional acetylcholine‐sensitivity in rat muscle maintained in organ culture

Purves¹,

Sakmann²

1974

127

SU2MMARY1. The effect of contractile activity on the initiation of spontaneous action potentials (fibrillation) and on extrajunctional acetylcholinesensitivity has been studied in single fibres in strips of previously denervated rat diaphragm maintained in organ culture for up to 10 days.2. Following removal of the diaphragm from the animal, fibrillation slowed and usually stopped altogether for about 24-36 hr. Thereafter, spontaneously active fibres were found in all cultured muscle strips.3. At any one time, about 4 to i of fibres impaled with micro-electrodes were active (defined as more than one action potential/10 sec), with a mean discharge frequency of 4.5/sec (range 0.1-24/sec).4. The duration of continuous activity in single fibres was, on average, 21-22 hr; a period of activity was followed by a longer inactive interval. Thus activity in;single fibres is cyclical.5. Direct stimulation of fibrillating strips for 24 hr at 10/sec suppressed spontaneous activity for 1-3 days.6. Conversely, blockade of spontaneous activity with tetrodotoxin for 72 hr led to a two-to threefold increase in the number of fibrillating fibres when the drug was washed out; in some strips nearly all fibres became spontaneously active.7. The mean rate of activity of diaphragm fibres during normal breathing, determined by recording single units from the phrenic nerve in lightly anaesthetized animals, is about 18/sec.

“…However, one cannot assume that cholinergic transmission plays an equivalent role D. B. DRACHMAN AND D. M. JOHNSTON in neurotrophic regulation of all properties of muscle. Indeed, there is now evidence that more than one factor is involved in the regulation of certain other properties of muscle, including ACh receptor distribution (Albuquerque, Warnick, Tasse & Sansone, 1972;Hofmann & Thesleff, 1972) and the localization of acetylcholinesterase (Drachman, 1972). Therefore each such property must be considered as a separate system, and the neurotrophic factors which influence it must be assessed quantitatively.…”

Section: Discussionmentioning

confidence: 99%

Neurotrophic regulation of dynamic properties of skeletal muscle: effects of botulinum toxin and denervation.

Drachman¹,

Johnston²

1975

SUMMARY1. In order to determine the role of acetylcholine (ACh) transmission in neurotrophic regulation of dynamic properties of muscle, the effects of botulinum toxin treatment were compared with those of denervation. The extensor digitorum longus (EDL) and soleus muscles of rats were either denervated or injected with botulinum toxin. At times up to 25 days the isometric properties of these muscles were determined.2. Both botulinum treatment and denervation produced progressive slowing of the time to peak of the twitch (TPT) and half-relaxation time of the twitch (ART), which was more pronounced in the EDL than in the soleus.3. Both treatments produced slowing of the relaxation curve following tetanic contraction, more marked in the EDL than in the soleus muscle. This indicates a slowing of relaxation, and suggests a prolongation of the active state of the muscle.4. The maximum rate of rise of the tetanus did not change significantly in the EDL and soleus muscles after botulinum treatment or denervation. This suggests that there is no major change in the speed of contraction under conditions of botulinum treatment or denervation.5. The changes produced by botulinum treatment and denervation were virtually identical in all parameters tested. This is interpreted meaning that cholinergic transmission (including muscle usage), or some other factor closely related to cholinergic transmission, accounts for the motor nerve's trophic influence in maintaining these dynamic properties of skeletal muscles.