A-Current Expression is Regulated by Activity but not by Target Tissues in Developing Lumbar Motoneurons of the Chick Embryo

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Abstract
The functional expression of A-type K+ channels ( IA) was examined in chick lumbar motoneurons (LMNs) at embryonic days 6 and 11 (E6 and E11). We observed a threefold increase in IA density between E6 and E11 in spinal cord slices and acutely dissociated LMNs. There was no change in current density, kinetics, or voltage dependence of IA in E11 homozygous limbless mutants or in E11 embryos in which hindlimbs were surgically removed at E6. Moreover, chronic in ovo administration of d-tubocurarine, which causes an increase in motoneuron branching on the surface of target muscles, had no effect on IA. Electrical activity played an important role in IA regulation in LMNs in vitro and in ovo. Blocking spontaneous electrical activity of LMNs by chronic in ovo application of mecamylamine or muscimol reduced IA by 80%. LMNs cultured in the presence of TTX also failed to express normal densities of IA, even when the cultures also contained target tissues. The portion of IA that remained after in ovo or in vitro blockade of activity inactivated more quickly than the IA of LMNs that were allowed to discharge spikes. The developmental expression of LMN IA increases significantly during development, and this increase is activity dependent but does not require interactions with target tissues. Ongoing activity also seems to regulate the kinetics of IA inactivation.