GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons.
Glial cell line-derived neurotrophic factor (GDNF) prevents lesion-induced death of midbrain dopaminergic neurons, but its function in normal brain remains uncertain. Here we show that GDNF acutely and reversibly potentiated the excitability of cultured midbrain neurons by inhibiting transient A-type K(+) channels. The effects of GDNF were limited to large, tyrosine hydroxylase (TH)-positive dopaminergic neurons, and were mediated by mitogen associated protein (MAP) kinase. Application of GDNF also elicited a MAP kinase-dependent enhancement of the excitability in dopaminergic neurons in midbrain slice. These results demonstrate an acute regulation of GDNF on ion channels and its underlying signaling mechanism, and reveal an unexpected role of GDNF in normal midbrain dopaminergic neurons.
Yang
F
F
Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China 200031.
Feng
L
L
Zheng
F
F
Johnson
S W
SW
Du
J
J
Shen
L
L
Wu
C P
CP
Lu
B
B
D015761:4-Aminopyridine / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine