beta -Neuregulin-1 is required for the in vivo development of functional Ca2+-activated K+ channels in parasympathetic neurons.

The development of functional Ca(2+)-activated K(+) channels (K(Ca)) in chick ciliary ganglion (CG) neurons requires interactions with afferent preganglionic nerve terminals. Here we show that the essential preganglionic differentiation factor is an isoform of beta-neuregulin-1. beta-Neuregulin-1 transcripts are expressed in the midbrain preganglionic Edinger-Westphal nucleus at developmental stages that coincide with or precede the normal onset of macroscopic K(Ca) in CG neurons. Injection of beta-neuregulin-1 peptide into the brains of developing embryos evoked a robust stimulation of functional K(Ca) channels at stages before the normal appearance of these channels in CG neurons developing in vivo. Conversely, injection of a neutralizing antiserum specific for beta-neuregulin-1 inhibited the development of K(Ca) channels in CG neurons. Low concentrations of beta-neuregulin-1 evoked a robust increase in whole-cell K(Ca) in CG neurons cocultured with iris target tissues. By contrast, culturing CG neurons with iris cells or low concentrations of beta-neuregulin-1 by themselves was insufficient to stimulate K(Ca). These data suggest that the preganglionic factor required for the development of K(Ca) in ciliary ganglion neurons is an isoform of beta-neuregulin-1, and that this factor acts in concert with target-derived trophic molecules to regulate the differentiation of excitability.

Posttranslational regulation of Ca(2+)-activated K+ currents by a target-derived factor in developing parasympathetic neurons.

Macroscopic IK[Ca is not expressed in normal levels in chick ciliary ganglion (CG) neurons prior to synapse formation with target tissues, or in neurons developing in vitro or in situ in the absence of target tissues. Here, two chick CG slo partial cDNAs encoding IK[Ca channels were isolated, cloned, and sequenced. Both slo transcripts were readily detected in developing CG neurons prior to or in the absence of target tissue interactions. When CG neurons developed in vitro in the presence of target tissue (iris) extracts, a normal whole-cell IK[Ca was expressed. These effects did not require protein synthesis, and the activity was detectable throughout the stages of synapse formation in the iris. The active component has an apparent molecular weight of 40-60 kDa.