Regulation of neuronal K(+) currents by target-derived factors: opposing actions of two different isoforms of TGFbeta.
The developmental expression of macroscopic Ca(2+)-activated K(+) currents in chick ciliary ganglion neurons is dependent on an avian ortholog of TGFbeta1, known as TGFbeta4, secreted from target tissues in the eye. Here we report that a different isoform, TGFbeta3, is also expressed in a target tissue of ciliary ganglion neurons. Application of TGFbeta3 inhibits the functional expression of whole-cell Ca(2+)-activated K(+) currents evoked by 12 hour treatment with either TGFbeta1 or beta-neuregulin-1 in ciliary ganglion neurons developing in vitro. TGFbeta3 had no effect on voltage-activated Ca(2+) currents. A neutralizing antiserum specific for TGFbeta3 potentiates stimulation of Ca(2+)-activated K(+) currents evoked by a target tissue (iris) extract in cultured ciliary ganglion neurons, indicating that TGFbeta3 is an inhibitory component of these extracts. Intraocular injection of TGFbeta3 causes a modest but significant inhibition of the expression of Ca(2+)-activated K(+) currents in ciliary ganglion neurons developing in vivo. Further, intraocular injection of a TGFbeta3-neutralizing antiserum stimulates expression of Ca(2+)-activated K(+) currents in ciliary ganglion neurons developing in vivo, indicating that endogenous TGFbeta3 regulates the functional expression of this current. The normal developmental expression of functional Ca(2+)-activated K(+) currents in ciliary ganglion neurons developing in vivo is therefore regulated by two different target-derived isoforms of TGFbeta, which produce opposing effects on the electrophysiological differentiation of these neurons.
Cameron
J S
JS
Department of Biology, University of Houston, Houston, TX 77204-5513, USA.
Dryer
L
L
Dryer
S E
SE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002642:Chick Embryo; D046508:Culture Techniques; D004594:Electrophysiology; D005724:Ganglia / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D007106:Immune Sera; D007498:Iris / Q000196:embryology* / Q000378:metabolism; D020880:Neuregulins; D009474:Neurons / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D020033:Protein Isoforms; D014020:Tissue Extracts; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D006023:Glycoproteins; D007106:Immune Sera; D020880:Neuregulins; D015221:Potassium Channels; D020033:Protein Isoforms; D014020:Tissue Extracts; D016212:Transforming Growth Factor beta; D002118:Calcium