Abstract
Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons1,2,3. They are also essential for modulating activity-dependent neuronal plasticity4,5,6,7. Here we show that neurotrophins elicit action potentials in central neurons. Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors8. Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.
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Acknowledgements
We thank R. Trautmann and E. Eilers for expert technical assistance and M. Ashdown for editorial assistance. This study was supported by a fellowship from the DFG to K.W.K. and by grants from the Deutsche Forschungsgemeinschaft and the Human Frontier Science Program to A.K.
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Kafitz, K., Rose, C., Thoenen, H. et al. Neurotrophin-evoked rapid excitation through TrkB receptors. Nature 401, 918–921 (1999). https://doi.org/10.1038/44847
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DOI: https://doi.org/10.1038/44847
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