PMID- 11593232
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20141120
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 4
IP  - 11
DP  - 2001 Nov
TI  - GDNF acutely modulates excitability and A-type K(+) channels in midbrain 
      dopaminergic neurons.
PG  - 1071-8
AB  - 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.
FAU - Yang, F
AU  - Yang F
AD  - Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China 200031.
FAU - Feng, L
AU  - Feng L
FAU - Zheng, F
AU  - Zheng F
FAU - Johnson, S W
AU  - Johnson SW
FAU - Du, J
AU  - Du J
FAU - Shen, L
AU  - Shen L
FAU - Wu, C P
AU  - Wu CP
FAU - Lu, B
AU  - Lu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Anesthetics, Local)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 66-40-0 (Tetraethylammonium)
RN  - BH3B64OKL9 (4-Aminopyridine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 4-Aminopyridine/pharmacology
MH  - Anesthetics, Local/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Culture Media, Serum-Free
MH  - Dopamine/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fluorescent Dyes/metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - In Vitro Techniques
MH  - Male
MH  - Membrane Potentials/physiology
MH  - Mesencephalon/*cytology/embryology
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Nerve Growth Factors/pharmacology
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Patch-Clamp Techniques
MH  - Potassium Channel Blockers/pharmacology
MH  - Potassium Channels, Voltage-Gated/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tetraethylammonium/pharmacology
MH  - Tetrodotoxin/pharmacology
EDAT- 2001/10/11 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/11 10:00
PHST- 2001/10/11 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/11 10:00 [entrez]
AID - nn734 [pii]
AID - 10.1038/nn734 [doi]
PST - ppublish
SO  - Nat Neurosci. 2001 Nov;4(11):1071-8. doi: 10.1038/nn734.