Rapid synthesis of acetylcholine receptors at neuromuscular junctions.
The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.
Ramsay
D A
DA
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
Drachman
D B
DB
Pestronk
A
A
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D005260:Female; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000096:biosynthesis*; D013997:Time Factors
D002038:Bungarotoxins; D011950:Receptors, Cholinergic