A-current expression is regulated by activity but not by target tissues in developing lumbar motoneurons of the chick embryo

The functional expression of A-type K+ channels (I-A) was examined in chick lumbar motoneurons (LMNs) at embryonic days 6 and 11 (E6 and E11). We observed a threefold increase in I-A 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 I-A 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 I-A. Electrical activity played an important role in I-A regulation in LMNs in vitro and in ovo. Blocking spontaneous electrical activity of LMNs by chronic in ovo application of mecamylamine or muscimol reduced I-A by 80%. LMNs cultured in the presence of TTX also failed to express normal densities of I-A, even when the cultures also contained target tissues. The portion of I-A that remained after in ovo or in vitro blockade of activity inactivated more quickly than the I-A of LMNs that were allowed to discharge spikes. The developmental expression of LMN I-A 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 I-A inactivation.