PMID- 10103109
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 11
IP  - 4
DP  - 1999 Apr
TI  - Selective up-regulation of P- and R-type Ca2+ channels in rat embryo motoneurons 
      by BDNF.
PG  - 1127-33
AB  - Cultured spinal cord motoneurons from day 15 rat embryos (E15) represent a useful 
      model to study Ca2+ channel diversities and their regulation by neurotrophins. 
      Besides the previously identified L-, N- and P-type channels, E15 rat motoneurons 
      also express high densities of R-type channels. We have previously shown that the 
      P-type channel is nearly absent in 60% of these cells, while the R-type 
      contributes to approximately 35% of the total current. Here, we show that chronic 
      preincubation of cultured rat motoneurons with high concentrations (20-100 ng/mL) 
      of brain-derived neurotrophic factor (BDNF) caused a selective up-regulation of 
      the P- and R-type current density available after blocking N- and L-type 
      channels, with no changes to cell membrane capacitance. N- and L-type channels 
      were either not affected or slightly down-modulated by the neurotrophin. The 
      onset of BDNF up-regulation of P/R-type currents had a half-time of 12 h and 
      reached maximal values of approximately 80%. High concentrations of nerve growth 
      factor (NGF; 50-100 ng/mL) had no effect on P/R currents, while BDNF action was 
      prevented by the kinase inhibitor K252a and by the protein synthesis inhibitor 
      anisomycin. These results suggest that chronic applications of BDNF selectively 
      up-regulates the Ca2+ channel types which are most likely to be involved in the 
      control of neurotransmitter release in mammalian neuromuscular junctions. The 
      signal transduction mechanism is probably mediated by TrkB receptors and involves 
      the synthesis of newly functionally active P- and R-type channels. Our data 
      furnish a rationale for a number of recent observations in other laboratories, in 
      which prolonged applications of neurotrophins were shown to potentiate the 
      presynaptic response in developing synapses.
FAU - Baldelli, P
AU  - Baldelli P
AD  - Department of Neuroscience, INFM, Research Unit, Turin, Italy.
FAU - Magnelli, V
AU  - Magnelli V
FAU - Carbone, E
AU  - Carbone E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channels)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Receptor, Ciliary Neurotrophic Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*pharmacology
MH  - Calcium Channels/*drug effects
MH  - Cells, Cultured
MH  - Embryo, Mammalian/drug effects
MH  - Motor Neurons/*drug effects
MH  - Patch-Clamp Techniques
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor Protein-Tyrosine Kinases/physiology
MH  - Receptor, Ciliary Neurotrophic Factor
MH  - Receptors, Nerve Growth Factor/physiology
MH  - Spinal Cord/cytology/*drug effects/embryology
MH  - Up-Regulation
EDAT- 1999/04/02 00:00
MHDA- 1999/04/02 00:01
CRDT- 1999/04/02 00:00
PHST- 1999/04/02 00:00 [pubmed]
PHST- 1999/04/02 00:01 [medline]
PHST- 1999/04/02 00:00 [entrez]
AID - 10.1046/j.1460-9568.1999.00523.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 1999 Apr;11(4):1127-33. doi: 10.1046/j.1460-9568.1999.00523.x.