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

The functional expression of Ca2+-activated K+ channels (K-Ca) in developing chick ciliary ganglion (CG) neurons requires interactions with target tissues and preganglionic innervation. Here, we show that the stimulatory effects of target tissues are mediated by an isoform of TGF beta. Exposure of cultured 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 extracts were blocked by a neutralizing pan-TGF beta antiserum but not by specific 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 differentiation factor expressed in preganglionic neurons.