Regulation of neuronal K+ currents by target-derived factors: opposing actions of two different isoforms of TGF beta

The developmental expression of macroscopic Ca2+-activated K+ currents in c hick ciliary ganglion neurons is dependent on an avian ortholog of TGF beta 1, known as TGF beta 4, secreted from target tissues in the eye. Here we r eport that a different isoform, TGF beta 3, is also expressed in a target t issue of ciliary ganglion neurons. Application of TGF beta 3 inhibits the f unctional expression of whole-cell Ca2+-activated K+ currents evoked by 12 hour treatment with either TGF beta 1 or beta-neuregulin-1 in ciliary gangl ion neurons developing in vitro. TGF beta 3 had no effect on voltage-activa ted Ca2+ currents. A neutralizing antiserum specific for TGF beta 3 potenti ates stimulation of Ca2+-activated K+ currents evoked by a target tissue (i ris) extract in cultured ciliary ganglion neurons, indicating that TGF beta 3 is an inhibitory component of these extracts. Intraocular injection of T GF beta 3 causes a modest but significant inhibition of the expression of C a2+-activated Kf currents in ciliary ganglion neurons developing in vivo. F urther, intraocular injection of a TGF beta 3-neutralizing antiserum stimul ates expression of Ca2+-activated K+ currents in ciliary ganglion neurons d eveloping in vivo, indicating that endogenous TGF beta 3 regulates the func tional expression of this current. The normal developmental expression of f unctional Ca2+-activated K+ currents in ciliary ganglion neurons developing in vivo is therefore regulated by two different target-derived isoforms of TGF beta, which produce opposing effects on the electrophysiological diffe rentiation of these neurons.