Postsynaptic target regulates functional responses induced by 5-HT3 serotonin receptors on axonal varicosities of NG108-15 hybrid neuroblastoma cells

Rat brain presynaptic 5-HT3 serotonin receptors. members of the ligand-gate d ion channel superfamily, induce changes in nerve terminal [Ca2+](i) in a manner distinct from that found for somatic 5-HT3 receptors. Here, we asses sed the role of postsynaptic target in regulating the nature of presynaptic receptor-induced responses, using the hybrid neuroblastoma cell line NG108 -15 as a model neuronal system that expresses 5-HT3 receptors. Using immuno cytochemistry, 5-HT3 receptors were found to be present on the presynaptic- like varicosities of differentiated NG108-15 cells, indicating that these r eceptors possess an inherent ability to localize to potential presynaptic s ites. In the absence of postsynaptic target, 5-HT3 receptors localized to t he varicosities induce rapid but transient changes in [Ca2+](i) that were i nitiated by voltage-gated Ca2+ channels, as assessed using Ca2+ channel blo ckers, these properties being typical of those found for somatic 5-HT3 rece ptors. In co-cultures containing rat myotubes, with which NG108-15 cells fo rm functional cholinergic synapses, the 5-HT3 receptor-induced changes in [ Ca2+](i) in the axonal varicosities shifted over time (three to 10 days) to that found for brain nerve endings: sustained responses that were insensit ive to blockade by antagonists of voltage-gated Ca2+ channels. The effect o f co-culturing myotubes with the NG108-15 cells was mimicked by conditioned media from myotube cultures. These results indicate that regulatory molecules from the target postsynapt ic cell dictate the functional responses elicited by presynaptic 5-HT3 rece ptors. Because the target-induced changes required several days before they were evident, we hypothesize that changes in protein expression, perhaps t he consequence of altered gene regulation, underlie the changes in the resp onses to 5-HT3 receptor activation in the axonal varicosities of this neuro nal cell line. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.