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

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Abstract
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 alpha‐bungarotoxin (I‐alpha BT); 1 day later the left hemidiaphragm was denervated. The degradation of bound I‐alpha BT in normal and denervated muscles was examined in organ culture, beginning at various times after denervation in vivo. 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. Muscles denervated only on transfer to organ culture also show an increase in the degradation rate of bound I‐alpha BT with increasing time of denervation (time in culture). In normal diaphragm muscles, the initial rate of degradation of functional ACh receptors, after correcting for non‐degradative loss of I‐alpha BT, is 0.0018 h‐1 (t1/2 = 383 h). The maximal rate at denervated end‐plates is 0.0073 h‐1 (t1/2 = 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 0.0005 h‐1 to 0.002 h‐1. The rate of loss of bound I‐alpha BT in vivo is more rapid at denervated end‐plates than at innervated end‐plates. For diaphragm muscles, the rates of I‐alpha BT degradation measured in organ culture are able to describe the relative rates of loss of I‐alpha BT from innervated and denervated muscles in vivo. At short times after labelling, a fraction (10‐20%) of the I‐alpha BT bound to innervated muscles is degraded more rapidly than the remaining toxin. The possibility that these I‐alpha BT binding sites are degraded at the rate characteristic of extrajunctional receptors on denervated muscle fibres is discussed.