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

Feng Yang; Linyin Feng; Bai Lu; Steven W. Johnson; Chien Ping Wu; Liya Shen

doi:10.1038/nn734

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

Feng Yang, Linyin Feng, Bai Lu, Steven W. Johnson, Chien Ping Wu, Liya Shen

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138 Scopus citations

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 language	English (US)
Pages (from-to)	1071-1078
Number of pages	8
Journal	Nature Neuroscience
Volume	4
Issue number	11
DOIs	https://doi.org/10.1038/nn734
State	Published - 2001
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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title = "GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons",

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.",

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AU - Feng, Linyin

AU - Lu, Bai

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AU - Wu, Chien Ping

AU - Shen, Liya

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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.

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

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