S L Shyng — Page 2 | PubMed Health

PubMed1990

Effect of reinnervation on the degradation rate of junctional acetylcholine receptors synthesized in denervated skeletal muscles.

Two populations of ACh receptors (AChRs) with different degradation rates have been shown to coexist in the postsynaptic membrane after denervation of the neuromuscular junction (NMJ). One population, consisting of the slowly degrading original AChRs inserted into the plasma membrane prior to denervation, has a degradation half-life (t1/2) of approximately 8 d. This degradation rate accelerates after denervation (to a t1/2 approximately 3 d), but can be decelerated back to the predenervation rate by reinnervation. The second population, the rapidly degrading new AChRs, which replace the degrading original AChRs at the NMJ after denervation, resembles embryonic AChRs, with a t1/2 of approximately 1 d. In the present study, we report that the degradation rate of these new junctional AChRs is unaltered for 3-6 half-lives after reinnervation. We further report that a small amount (less than 10%) of slowly degrading AChRs (t1/2 approximately 3 d) may also be synthesized in denervated muscle. We suggest that, unlike its effect on the original, slowly degrading AChRs, reinnervation does not modulate the degradation rate of the rapidly degrading new junctional AChRs. It merely regulates the ratio of rapidly to slowly degrading AChRs being synthesized and inserted at the NMJ.

Animals↗

PubMed1989

Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions.

Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation (referred to as original receptors). No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates. The progressive increase in turnover rate of total AChRs therefore reflects the combined rates of the original and new receptors, as earlier postulated by Levitt and Salpeter (1981).

Animals↗