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.
Cameron
J S
JS
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.
Dryer
L
L
Dryer
S E
SE
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D018920:Coculture Techniques; D017931:DNA Primers; D018076:DNA, Complementary; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D018076:DNA, Complementary; D020890:Neuregulin-1; D015221:Potassium Channels; D012333:RNA, Messenger; D002118:Calcium