Denervated endplates have a dual population of junctional acetylcholine receptors

Abstract

The acetylcholine receptors (AChRs) at the neuromuscular junctions of mature innervated muscle are distinguished, in part, from extrajunctional receptors of embryonic muscle fibres by their metabolic stability^1–5 and high concentration at the tops of the postjunctional folds^6,7. After denervation, the rate of degradation of receptors at the neuromuscular junction progressively increases^8–12 even though their local concentration does not change^7,8,11. Two alternatives suggest themselves—there may be a simultaneous, progressive increase in degradation rate of all junctional receptors after denervation, or the increase may reflect the composite behaviour of two populations of junctional receptors with different metabolic stabilities: those existing before denervation (‘original AChRs’) and those inserted afterwards (‘new AChRs’). Our study has been designed to distinguish between these possibilities. We have now found that up to 8–10 days after denervation, the original receptors have a degradation half life of about 8 days which is indistinguishable from that of innervated junctional receptors. After that time, their degradation half life increases to about 2.5 days. However, all new AChRs, introduced at junctional sites after denervation, have a half life characteristic of extrajunctional receptors (about 1 day). Our data thus support the hypothesis of a composite population of receptors at denervated neuromuscular junctions.