title: Developmental changes in the half-life of acetylcholine receptors in the myotomal muscle of Xenopus laevis.
abstract: 1. Tail preparations, containing myotomal muscle and associated spinal cord, were isolated from embryos and tadpoles of Xenopus laevis between stages 25 and 49 (1.15-12 days) and were pulse-labelled with 125I-alpha-bungarotoxin (125I alpha BT) so that the half-life (T1/2) of their acetylcholine receptors (AChRs) could be estimated in organ culture. 2. For the entire population of AChRs, estimates of T1/2 based on a single exponential decline in radioactivity (but see item 4 below) increased from 53-55 h at stages 25-31 (1.15-1.56 days) to approximately 135 h at stage 47 (5.5 days). Beyond stage 47 T1/2 increased only slightly. 3. Radioautographic estimates of the T1/2 of extrajunctional AChRs at stages 47-48 (5.5-7.5 days) were 41-50 h. It follows that the developmental change in the T1/2 of the entire population of AChRs was due to the junctional AChRs. 4. At stages 47-49 (5.5-12 days) the decline in radioactivity for the entire population of AChRs was fitted well by a double exponential. Assuming a T1/2 of 50 h for the extrajunctional AChRs and 210 h for the junctional AChRs, the correlation coefficient (r) was 0.9947 +/- 0.0014 (mean +/- S.E.M.; n = 14) and junctional AChRs were estimated to comprise 80 +/- 3% of the entire population. Similar analysis, as well as experiments in which the degradation of junctional AChRs was assessed by pulse-labelling with fluorescent alpha-bungarotoxin, suggested that at earlier stages of development the junctional AChRs have a shorter T1/2 and comprise a smaller fraction of the entire population. 5. The developmental increase in T1/2 occurred even when animals were raised in the anaesthetic tricaine or in tetrodotoxin, conditions which abolished all motor activity. 6. Developmental increases in T1/2 also occurred in culture but were smaller than those in vivo. The increases in culture did not occur amongst those AChRs which were pre-labelled with 125I alpha BT. 7. It is concluded that in Xenopus myotomal muscle the T1/2 of junctional AChRs begins to increase within a day after the onset of innervation and that the increase does not require nerve or muscle impulse activity. We suggest, among other possibilities, that it may depend upon incorporation of a different molecular species of AChR into the postsynaptic membrane.
authors.affiliation: Department of Physiology, McGill University, Montreal, Quebec, Canada.
authors.forename: M W
authors.initials: MW
authors.lastname: Cohen
authors.forename: P F
authors.initials: PF
authors.lastname: Frair
authors.forename: C
authors.initials: C
authors.lastname: Cantin
authors.forename: G
authors.initials: G
authors.lastname: Hébert
mesh_terms: D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D006207:Half-Life; D007814:Larva; D009043:Motor Activity / Q000187:drug effects; D009132:Muscles / Q000378:metabolism*; D009924:Organ Culture Techniques; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: D062365:Aminobenzoates; D002038:Bungarotoxins; D011950:Receptors, Cholinergic; C003636:tricaine; D013779:Tetrodotoxin