Se. Dryer, ROLE OF CELL-CELL INTERACTIONS IN THE DEVELOPMENTAL REGULATION OF CA2(-ACTIVATED K+ CURRENTS IN VERTEBRATE NEURONS()), Journal of neurobiology, 37(1), 1998, pp. 23-36
The functional expression of the Ca2+-activated K+ current (I-K[Ca]) i
s dependent on cell-cell interactions in developing chick autonomic ne
urons. In chick ciliary ganglion (CG) neurons, expression of macroscop
ic I-K[Ca] coincides with the formation of synapses with target tissue
s. CG neurons that develop in vivo in the absence of normal target tis
sues fail to express functional I-K[Ca], although voltage-activated Ca
2+ currents and most other ionic currents are expressed at normal ampl
itudes and densities. CG neurons placed in cell culture prior to forma
tion of synapses with target tissues also fail to express macroscopic
I-K[Ca]. However, CG neurons cultured in the presence of a heat- and t
rypsin-sensitive extract of target tissues express I-K[Ca] at normal l
evels. Similarly, interactions with target tissue appear to regulate t
he expression of whole-cell I-K[Ca] in developing chick sympathetic ga
nglion neurons, although the relevant trophic factors appear to be dif
ferent from those required by CG neurons. In addition to target tissue
interactions, an intact preganglionic innervation is required for the
normal in vivo development of I-K[Ca] in chick CG neurons. The trophi
c effects of the afferent innervation do not require synaptic activati
on of the CG neurons, indicating secretion of a trophic factor, possib
ly an isoform of beta-neuregulin. The results are consistent with the
hypothesis that target- and nerve terminal-derived trophic factors int
eract at a posttranslational level in the regulation of a functional I
-K[Ca]. Together, this body of data demonstrates an essential role for
cell-cell interactions in the differentiation of neuronal excitabilit
y. (C) 1998 John Wiley & Sons, Inc.