Developmental regulation of neuronal K+ channels by target-derived TGF beta in vivo and in vitro

The functional expression of Ca2+-activated K+ channels (K-Ca) in developin g chick ciliary ganglion (CG) neurons requires interactions with target tis sues and preganglionic innervation. Here, we show that the stimulatory effe cts of target tissues are mediated by an isoform of TGF beta. Exposure of c ultured CG neurons to TGF beta 1, but not TGF beta 2 or TGF beta 3, caused robust stimulation of K-Ca. The K-Ca stimulatory effects of target tissue e xtracts were blocked by a neutralizing pan-TGF beta antiserum but not by sp ecific TGF beta 2 or TGF beta 3 antisera. Intraocular injection of TGF beta 1 caused robust stimulation of K-Ca, whereas intraocular injection of pan- TGF beta antiserum inhibited expression of K-Ca in CG neurons developing in vivo. The effects of TGF beta 1 were potentiated by beta-neuregulin-1, a d ifferentiation factor expressed in preganglionic neurons.