GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons

Feng Yang, Linyin Feng, Fang Zheng, Steven Johnson, Jing Du, Liya Shen, Chien Ping Wu, Bai Lu

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalNature Neuroscience
Volume4
Issue number11
DOIs
StatePublished - 2001
Externally publishedYes

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Glial Cell Line-Derived Neurotrophic Factor
Dopaminergic Neurons
Mesencephalon
Mitogens
Protein Kinases
Tyrosine 3-Monooxygenase
Ion Channels
Neurons
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons. / Yang, Feng; Feng, Linyin; Zheng, Fang; Johnson, Steven; Du, Jing; Shen, Liya; Wu, Chien Ping; Lu, Bai.

In: Nature Neuroscience, Vol. 4, No. 11, 2001, p. 1071-1078.

Research output: Contribution to journalArticle

Yang, F, Feng, L, Zheng, F, Johnson, S, Du, J, Shen, L, Wu, CP & Lu, B 2001, 'GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons', Nature Neuroscience, vol. 4, no. 11, pp. 1071-1078. https://doi.org/10.1038/nn734
Yang, Feng ; Feng, Linyin ; Zheng, Fang ; Johnson, Steven ; Du, Jing ; Shen, Liya ; Wu, Chien Ping ; Lu, Bai. / GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons. In: Nature Neuroscience. 2001 ; Vol. 4, No. 11. pp. 1071-1078.
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