title: Brain-derived neurotrophic factor inhibits calcium channel activation, exocytosis, and endocytosis at a central nerve terminal.
abstract: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic function and plasticity and plays important roles in neuronal development, survival, and brain disorders. Despite such diverse and important roles, how BDNF, or more generally speaking, neurotrophins affect synapses, particularly nerve terminals, remains unclear. By measuring calcium currents and membrane capacitance during depolarization at a large mammalian central nerve terminal, the rat calyx of Held, we report for the first time that BDNF slows down calcium channel activation, including P/Q-type channels, and inhibits exocytosis induced by brief depolarization or single action potentials, inhibits slow and rapid endocytosis, and inhibits vesicle mobilization to the readily releasable pool. These presynaptic mechanisms may contribute to the important roles of BDNF in regulating synapses and neuronal circuits and suggest that regulation of presynaptic calcium channels, exocytosis, and endocytosis are potential mechanisms by which neurotrophins achieve diverse neuronal functions.
authors: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
authors: Maryna
authors: M
authors: Baydyuk
authors: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
authors: Xin-Sheng
authors: XS
authors: Wu
authors: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
authors: Liming
authors: L
authors: He
authors: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892 wul@ninds.nih.gov.
authors: Ling-Gang
authors: LG
authors: Wu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002120:Calcium Channel Agonists
keywords: BDNF; calcium channels; calyx of Held; endocytosis; exocytosis