Neurotrophin-evoked rapid excitation through TrkB receptors.
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.
Kafitz
K W
KW
Institut für Physiologic, Technische Universität München, Germany.
Rose
C R
CR
Thoenen
H
H
Konnerth
A
A
D000200:Action Potentials; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008564:Membrane Potentials; D009414:Nerve Growth Factors / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D015222:Sodium Channels; D018698:Glutamic Acid; C049985:staurosporine aglycone; D020813:Receptor, trkB; D002118:Calcium