title: CNTF-evoked activation of JAK and ERK mediates the functional expression of T-type Ca2+ channels in chicken nodose neurons.
abstract: Culture of chicken nodose neurons with CNTF but not BDNF causes a significant increase in T-type Ca(2+) channel expression. CNTF-induced channel expression requires 12 h stimulation to reach maximal expression and is not affected by inhibition of protein synthesis, suggesting the involvement of a post-translational mechanism. In this study, we have investigated the biochemical mechanism responsible for the CNTF-dependent stimulation of T-type channel expression in nodose neurons. Stimulation of nodose neurons with CNTF evoked a considerable increase in signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK) phosphorylation. CNTF-evoked ERK phosphorylation was transient whereas BDNF-evoked activation of ERK was sustained. Pre-treatment of nodose neurons with the Janus tyrosine kinase (JAK) inhibitor P6 blocked STAT3 and ERK phosphorylation, whereas the ERK inhibitor U0126 prevented ERK activation but not STAT3 phosphorylation. Both P6 and U0126 inhibited the stimulatory effect of CNTF on T-type channel expression. Inhibition of STAT3 activation by the selective blocker stattic has no effect on ERK phosphorylation and T-type channel expression. These results indicate that CNTF-evoked stimulation of T-type Ca(2+) channel expression in chicken nodose neurons requires JAK-dependent ERK signaling. A cardiac tissue extract derived from E20 chicken heart was also effective in promoting T-type Ca(2+) channel expression and STAT3 and ERK phosphorylation. The ability of the heart extract to stimulate JAK/STAT and ERK activation was developmentally regulated. These findings provide further support to the idea that CNTF or a CNTF-like factor mediates normal expression of T-type channels.
authors.affiliation: Department of Biology, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Trimarchi
authors.forename: Judith
authors.initials: J
authors.lastname: Pachuau
authors.forename: Andrew
authors.initials: A
authors.lastname: Shepherd
authors.forename: Deblina
authors.initials: D
authors.lastname: Dey
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin-Caraballo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020747:Calcium Channels, T-Type; D020934:Ciliary Neurotrophic Factor; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit; D004791:Enzyme Inhibitors; D050796:STAT3 Transcription Factor; D053612:Janus Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium