title: Glial cell line-derived neurotrophic factor acutely modulates the excitability of rat small-diameter trigeminal ganglion neurons innervating facial skin.
abstract: Glial cell line-derived neurotrophic factor (GDNF) plays an important role in adult sensory neuron function. However, the acute effects of GDNF on primary sensory neuron excitability remain to be elucidated. The aim of the present study was to investigate whether GDNF acutely modulates the excitability of adult rat trigeminal ganglion (TRG) neurons that innervate the facial skin by using perforated-patch clamping, retrograde-labeling and immunohistochemistry techniques. Fluorogold (FG) retrograde labeling was used to identify the TRG neurons innervating the facial skin. The FG-labeled small- and medium-diameter GDNF immunoreactive TRG neurons, and most of these neurons also expressed the GDNF family receptor alpha-1 (GFRalpha-1). In whole-cell voltage-clamp mode, GDNF application significantly inhibited voltage-gated K(+) transient (I(A)) and sustained (I(K)) currents in most dissociated FG-labeled small-diameter TRG neurons. This effect was concentration-dependent and was abolished by co-application of the protein tyrosine kinase inhibitor, K252b. Under current-clamp conditions, the repetitive firing during a depolarizing pulse were significantly increased by GDNF application. GDNF application also increased the duration of the repolarization phase and decreased the duration of the depolarization phase of the action potential, and these characteristic effects were also abolished by co-application of K252b. These results suggest that acute application of GDNF enhances the neuronal excitability of adult rat small-diameter TRG neurons innervating the facial skin, via activation of GDNF-induced intracellular signaling pathway. We therefore conclude that a local release of GDNF from TRG neuronal soma and/or nerve terminals may regulate normal sensory function, including nociception.
authors.affiliation: Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan. m-takeda@tokyo.ndu.ac.jp
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitagawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Nasu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
authors.forename: Shigeji
authors.initials: S
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D004594:Electrophysiology; D005145:Face / Q000294:innervation*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000294:innervation*; D009435:Synaptic Transmission / Q000187:drug effects; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure*
chemical_list: D002227:Carbazoles; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007202:Indicators and Reagents; D026121:Indole Alkaloids; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; C049985:staurosporine aglycone