ROLE OF CELL-CELL INTERACTIONS IN THE DEVELOPMENTAL REGULATION OF CA2(-ACTIVATED K+ CURRENTS IN VERTEBRATE NEURONS())

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.