PMID- 10553907 OWN - NLM STAT- MEDLINE DCOM- 19991124 LR - 20220331 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 401 IP - 6756 DP - 1999 Oct 28 TI - Neurotrophin-evoked rapid excitation through TrkB receptors. PG - 918-21 AB - Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons. They are also essential for modulating activity-dependent neuronal plasticity. 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 receptors. 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. FAU - Kafitz, K W AU - Kafitz KW AD - Institut fur Physiologic, Technische Universitat Munchen, Germany. FAU - Rose, C R AU - Rose CR FAU - Thoenen, H AU - Thoenen H FAU - Konnerth, A AU - Konnerth A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Indole Alkaloids) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotransmitter Agents) RN - 0 (Sodium Channels) RN - 3KX376GY7L (Glutamic Acid) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor, trkB) RN - SY7Q814VUP (Calcium) SB - IM CIN - Nature. 1999 Oct 28;401(6756):862-3. PMID: 10553898 MH - Action Potentials MH - Animals MH - Brain-Derived Neurotrophic Factor/physiology MH - Calcium/metabolism MH - Carbazoles/pharmacology MH - Glutamic Acid/physiology MH - In Vitro Techniques MH - Indole Alkaloids MH - Membrane Potentials MH - Nerve Growth Factors/*physiology MH - Neurotransmitter Agents/physiology MH - Patch-Clamp Techniques MH - Pyramidal Cells/physiology MH - Rats MH - Rats, Wistar MH - Receptor, trkB/*physiology MH - Sodium Channels/physiology MH - Synaptic Transmission/*physiology EDAT- 1999/11/30 09:00 MHDA- 2001/03/23 10:01 CRDT- 1999/11/30 09:00 PHST- 1999/11/30 09:00 [pubmed] PHST- 2001/03/23 10:01 [medline] PHST- 1999/11/30 09:00 [entrez] AID - 10.1038/44847 [doi] PST - ppublish SO - Nature. 1999 Oct 28;401(6756):918-21. doi: 10.1038/44847.