Developmental Regulation of Neuronal K+ Channels by Target-Derived TGFβ In Vivo and In Vitro

Abstract

The functional expression of Ca2+-activated K+ channels (KCa) 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 TGFβ. Exposure of cultured CG neurons to TGFβ1, but not TGFβ2 or TGFβ3, caused robust stimulation of KCa. The KCa stimulatory effects of target tissue extracts were blocked by a neutralizing pan-TGFβ antiserum but not by specific TGFβ2 or TGFβ3 antisera. Intraocular injection of TGFβ1 caused robust stimulation of KCa, whereas intraocular injection of pan-TGFβ antiserum inhibited expression of KCa in CG neurons developing in vivo. The effects of TGFβ1 were potentiated by β-neuregulin-1, a differentiation factor expressed in preganglionic neurons.