PMID- 10811820
OWN - NLM
STAT- MEDLINE
DCOM- 20000615
LR  - 20191210
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 149
IP  - 4
DP  - 2000 May 15
TI  - Intracellular Ca(2+) and Ca(2+)/calmodulin-dependent kinase II mediate acute 
      potentiation of neurotransmitter release by neurotrophin-3.
PG  - 783-92
AB  - Neurotrophins have been shown to acutely modulate synaptic transmission in a 
      variety of systems, but the underlying signaling mechanisms remain unclear. Here 
      we provide evidence for an unusual mechanism that mediates synaptic potentiation 
      at the neuromuscular junction (NMJ) induced by neurotrophin-3 (NT3), using 
      Xenopus nerve-muscle co-culture. Unlike brain-derived neurotrophic factor (BDNF), 
      which requires Ca(2+) influx for its acute effect, NT3 rapidly enhances 
      spontaneous transmitter release at the developing NMJ even when Ca(2+) influx is 
      completely blocked, suggesting that the NT3 effect is independent of 
      extracellular Ca(2+). Depletion of intracellular Ca(2+) stores, or blockade of 
      inositol 1, 4, 5-trisphosphate (IP3) or ryanodine receptors, prevents the 
      NT3-induced synaptic potentiation. Blockade of IP3 receptors can not prevent 
      BDNF-induced potentiation, suggesting that BDNF and NT3 use different mechanisms 
      to potentiate transmitter release. Inhibition of Ca(2+)/calmodulin-dependent 
      kinase II (CaMKII) completely blocks the acute effect of NT3. Furthermore, the 
      NT3-induced potentiation requires a continuous activation of CaMKII, because 
      application of the CaMKII inhibitor KN62 reverses the previously established NT3 
      effect. Thus, NT3 potentiates neurotransmitter secretion by stimulating Ca(2+) 
      release from intracellular stores through IP3 and/or ryanodine receptors, leading 
      to an activation of CaMKII.
FAU - He, X
AU  - He X
AD  - Unit on Synapse Development and Plasticity, National Institute of Child Health 
      and Human Development, National Institutes of Health, Bethesda, Maryland 20892, 
      USA.
FAU - Yang, F
AU  - Yang F
FAU - Xie, Z
AU  - Xie Z
FAU - Lu, B
AU  - Lu B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CAMK2N2 protein, human)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Carrier Proteins)
RN  - 0 (ITPR1 protein, human)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Carrier Proteins
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Electric Conductivity
MH  - Enzyme Activation
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Intracellular Signaling Peptides and Proteins
MH  - Neuromuscular Junction/physiology
MH  - Neurotransmitter Agents/*metabolism
MH  - Neurotrophin 3/*pharmacology
MH  - Patch-Clamp Techniques
MH  - Presynaptic Terminals/physiology
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Ryanodine Receptor Calcium Release Channel/metabolism
MH  - Synaptic Transmission/*physiology
MH  - Xenopus
PMC - PMC2174561
EDAT- 2000/05/17 09:00
MHDA- 2000/06/17 09:00
PMCR- 2000/11/15
CRDT- 2000/05/17 09:00
PHST- 2000/05/17 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/05/17 09:00 [entrez]
PHST- 2000/11/15 00:00 [pmc-release]
AID - 0002067 [pii]
AID - 10.1083/jcb.149.4.783 [doi]
PST - ppublish
SO  - J Cell Biol. 2000 May 15;149(4):783-92. doi: 10.1083/jcb.149.4.783.