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Ischemic Stroke

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（三） Dear Editor, We would like to submit the enclosed manuscript entitled "GDNF Acutely Modulates Neuronal Excitability

and A-type Potassium Channels in Midbrain Dopaminergic Neurons", which we wish to be considered for

publication in Nature Neuroscience. GDNF has long been thought to be a potent neurotrophic factor for the survival of midbrain dopaminergic

neurons, which are degenerated in Parkinson s disease. In this paper, we report an unexpected, acute

effect of GDNF on A-type potassium channels, leading to a potentiation of neuronal excitability, in the

dopaminergic neurons in culture as well as in adult brain slices. Further, we show that GDNF regulates the K+ channels through a mechanism that involves activation of MAP kinase. Thus, this study has revealed,

for the first time, an acute modulation of ion channels by GDNF. Our findings challenge the classic view of

GDNF as a long-term survival factor for midbrain dopaminergic neurons, and suggest that the normal

function of GDNF is to regulate neuronal excitability, and consequently dopamine release. These results