Rochlin_1990_Dev.Biol_140_27

Nerve, polycation-coated beads, and electric fields not only induce acetylcholine receptors (AChRs) to cluster, but they also reduce the number of spontaneous AChR patches (hotspots) away from the induced cluster sites on embryonic Xenopus myotomal muscle cells grown in tissue culture (the global effect). In vivo, the ability of an AChR clustering stimulus to depress cluster formation elsewhere on the muscle cell may influence both the site at which the neuromuscular junction develops as well as which axons survive during synapse elimination. Since the causes of hotspot formation may be variable and cannot be controlled, we have further characterized the global effect by using AChR-clustering stimuli that can be controlled by the experimenter. We report that innervation inhibits the formation and maintenance of bead-associated AChR patches (BARPs) by a percentage of polycation-coated beads. We next investigated competition between beads and between beads and electric fields. In competition between beads added to the muscle cells at different times, however, the first set of beads had a competitive advantage over the second set of beads. This advantage was strengthened when the latency between bead applications was extended, or when a relatively large number of BARPs were formed by the first set of beads. Likewise, long-term electric fields were able to prevent the formation of BARPs, but were unable to disperse mature BARPs. Longer electric fields, or electric fields of greater magnitude competed better with the beads than brief or weak field treatments. None of the "winning" stimuli, including nerve, were able to totally block AChR patch formation or maintenance by competing stimuli. Thus, the global effect, at least in the case of competition between nonneuronal stimuli, favors the initial stimulus and appears to be graded.