Junctional form of acetylcholinesterase restored at nerve-free endplates

SUMMARY1. We have studied the effect of denervation on the degradation of the existing junctional acetylcholine (ACh) receptors at end-plates in rat muscles. ACh receptors were labelled by injecting animals with iodinated a-bungarotoxin (I-aBT); 1 day later the left hemidiaphragm was denervated. The degradation of bound I-aBT in normal and denervated muscles was examined in organ culture, beginning at various times after denervation in vivo.2. The original, pre-labelled end-plate ACh receptors are degraded more rapidly after denervation. The rate of degradation begins to increase shortly after the nerve is cut and reaches a maximum value at about 9 days of denervation.3. Muscles denerva~ted only on transfer to organ culture also show an increase in the degradation rate of bound I-aBT with increasing time of denervation (time in culture).4. In normal diaphragm muscles, the initial rate of degradation of functional ACh receptors, after correcting for non-degradative loss of I-aBT, is 010018 h-1 (tj = 383 h). The maximal rate at denervated end-plates is 010073 h-1 (tj = 94 h). For soleus, sternomastoid, plantaris and intercostal innervated muscles the apparent rate of ACh receptor degradation either in vitro or in vivo ranged from 010005 h-1 to 0-002 h-1. 5. The rate of loss of bound I-aBT in vivo is more rapid at denervated end-plates than at innervated end-plates. For diaphragm muscles, the rates ofI-acBT degradation measured in organ culture are able to describe the relative rates of loss of I-aBT from innervated and denervated muscles in vivo.6. At short times after labelling, a fraction (10-20%) of the I-BT bound to innervated muscles is degraded more rapidly than the remaining toxin. The possibility that these I-BT binding sites are degraded at the rate characteristic of extrajunctional receptors on denervated muscle fibres is discussed.

“…It has been reported that the 16 S, end-plate-specific form of acetylcholinesterase is rapidly lost after denervation (Vigny, Koenig & Rieger, 1976;Weinberg & Hall, 1979).…”

Section: Discussionmentioning

confidence: 99%

Denervation increases the degradation rate of acetylcholine receptors at end‐plates in vivo and in vitro.

Bevan¹,

Steinbach²

1983

“…Based on the results in denervated mouse muscle (Ko et al 1977), however, it seems likely that patches of receptor-rich membrane appear before the ChE activity is high enough to detect histochemically. Short term denervation of rodent muscle results in the loss of all detectable 16S (junctional specific) AChE from the muscle within 14 days (Vigny, Koenig & Rieger, 1976;Weinberg & Hall, 1979;Fernandez, Duell & Festaff, 1979), although an accumulation of AChE activity is demonstrable at denervated junctions for at least 56 days (Guth, Albers & Brown, 1964). If the results from rodent muscle are applicable to denervated cat muscle, the esterase staining on denervated cat muscle fibres is due to AChE activity, but probably the enzyme is not the 16S (junctional) form.…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular junctions and alpha‐bungarotoxin‐binding sites in denervated and contralateral cat skeletal muscles.

Steinbach¹

1981

SUMMARY1. The distributions of cholinesterase (ChE) activity and acetylcholine (ACh) receptors were studied in normal and denervated cat hind-limb fast-twitch skeletal muscles and in muscles contralateral to denervated muscles.2. On normal muscle fibres almost all receptors were confined to the immediately post-junctional membrane, although a perijunctional gradient of increased ACh receptor density was found on both fast-and slow-twitch fibres. After denervation, the extrajunctional ACh receptor density increased greatly and remained high for at least 10 months. Ectopic regions staining for ChE activity and having a high density of ACh receptors appeared in denervated muscle. The number of junctional ACh receptors decreased slowly after denervation, with a half-time of about 140 days.3. Fast-twitch muscles contralateral to denervated muscles also showed changes, including an increase in junctional size and a small but significant increase in extrajunctional ACh receptor density.

“…The interpretation is more complicated, however, because it is not clear why the ChE activity remained while ACh receptor density decreased. In adult rat muscle both the ChE activity and ACh receptor accumulation at denervated junctions can be preserved by ectopic innervation (Guth, Zalewski & Brown, 1966;Frank, Gautvick & Sommerschild, 1975;Weinberg & Hall, 1979). It is likely that the ChE-staining regions had been innervated at one time, because the ChE deposits resembled junctional deposits.…”

Section: Innervationmentioning

confidence: 99%

Alterations in cat skeletal neuromuscular junctions following prolonged inactivity.

Eldridge¹,

Liebhold²,

Steinbach³

1981

1. The distributions of acetylcholine (ACh) receptors, cholinesterase (ChE) activity and nerve terminals were studied on cat muscle fibres which had been inactive for 2‐3 years. 2. Neuromuscular junctions increased in size as a result of sprouting of terminal branches. In addition some fibres were multiply innervated at separate sites. 3. In muscles from two cats, some areas at the junction showed ChE activity but had only a relatively low density of ACh receptors. 4. The extrajunctional receptor density was higher than in normal muscles but lower than in muscles denervated for up to 10 months.