Nonjunctional acetylcholine receptor channel open time decreases during development of Xenopus muscle

Abstract

The mean channel open time of junctional acetylcholine receptors (AChRs) decreases during development of mammalian skeletal neuromuscular junctions^1–3. The junctional AChRs of newborn rats have long mean channel open times of about 4.5 ms and in this respect are similar to nonjunctional AChRs of adult denervated muscle^3–5. Mature neuromuscular junctions have channels with shorter mean open times of about 1 ms, whereas junctions at intermediate stages seem to have a mixture of channels with short and long open times^1–3. These observations, taken together with findings on receptor distribution during development^6,14, suggest that the establishment of nerve–muscle contact induces an aggregation of embryonic AChRs with long mean channel open times at the point of contact and that these embryonic junctional receptors are then replaced, modified or subjected to local membrane changes leading to a discrete reduction in channel open time. However, the fate of those embryonic nonjunctional receptors which are not aggregated at the newly formed neuromuscular junction is unknown. Are they an unchanging population, or do the changes in kinetic behaviour which occur at the junctional regions also take place at other regions of the muscle membrane? The kinetics of nonjunctional receptors in mammalian skeletal muscle have not been studied during development. We have now, however, examined this question in amphibian myotomal muscle, where nonjunctional receptors are present in substantial numbers throughout development, making it possible to measure the mean open time of both classes of AChR channel. We observed a shortening of mean channel open time of junctional AChRs, from about 3 ms to 1 ms, and an identical change in mean channel open time of AChRs at nonjunctional regions of membrane.