BDNF-Induced potentiation of spontaneous twitching in innervated myocytes requires calcium release from intracellular stores.
Brain-derived neurotrophic factor (BDNF) can potentiate synaptic release at newly developed frog neuromuscular junctions. Although this potentiation depends on extracellular Ca(2+) and reflects changes in acetylcholine release, little is known about the intracellular transduction or calcium signaling pathways. We have developed a video assay for neurotrophin-induced potentiation of myocyte twitching as a measure of potentiation of synaptic activity. We use this assay to show that BDNF-induced synaptic potentiation is not blocked by cadmium, indicating that Ca(2+) influx through voltage-gated Ca(2+) channels is not required. TrkB autophosphorylation is not blocked in Ca(2+)-free conditions, indicating that TrkB activity is not Ca(2+) dependent. Additionally, an inhibitor of phospholipase C interferes with BDNF-induced potentiation. These results suggest that activation of the TrkB receptor activates phospholipase C to initiate intracellular Ca(2+) release from stores which subsequently potentiates transmitter release.
Kleiman
R J
RJ
Department of Physiology, University of California, San Francisco, California 94143-0723, USA.
Tian
N
N
Krizaj
D
D
Hwang
T N
TN
Copenhagen
D R
DR
Reichardt
L F
LF
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D009046:Motor Neurons / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D016716:PC12 Cells; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D020813:Receptor, trkB / Q000502:physiology; D013569:Synapses / Q000201:enzymology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014981:Xenopus
D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D002104:Cadmium; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019000:Phosphotyrosine; D014443:Tyrosine; D019284:Thapsigargin; D020813:Receptor, trkB; D010738:Type C Phospholipases; D002118:Calcium; C000543:cyclopiazonic acid