PMID- 19403809
OWN - NLM
STAT- MEDLINE
DCOM- 20090603
LR  - 20220309
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 29
IP  - 17
DP  - 2009 Apr 29
TI  - p75 and TrkA signaling regulates sympathetic neuronal firing patterns via 
      differential modulation of voltage-gated currents.
PG  - 5411-24
LID - 10.1523/JNEUROSCI.3503-08.2009 [doi]
AB  - Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic 
      factor (BDNF) act through the tropomyosin-related receptor tyrosine kinases (Trk) 
      and the pan-neurotrophin receptor (p75) to regulate complex developmental and 
      functional properties of neurons. While NGF activates both receptor types in 
      sympathetic neurons, differential signaling through TrkA and p75 can result in 
      widely divergent functional outputs for neuronal survival, growth, and synaptic 
      function. Here we show that TrkA and p75 signaling pathways have opposing effects 
      on the firing properties of sympathetic neurons, and define a mechanism whereby 
      the relative level of signaling through these two receptors sets firing patterns 
      via coordinate regulation of a set of ionic currents. We show that signaling 
      through the p75 pathway causes sympathetic neurons to fire in a phasic pattern 
      showing marked accommodation. Signaling through the NGF-specific TrkA, on the 
      other hand, causes cells to fire tonically. Neurons switch rapidly between firing 
      patterns, on the order of minutes to hours. We show that changes in firing 
      patterns are caused by neurotrophin-dependent regulation of at least four 
      voltage-gated currents: the sodium current and the M-type, delayed rectifier, and 
      calcium-dependent potassium currents. Neurotrophin release, and thus receptor 
      activation, varies among somatic tissues and physiological state. Thus, these 
      data suggest that target-derived neurotrophins may be an important determinant of 
      the characteristic electrical properties of sympathetic neurons and therefore 
      regulate the functional output of the sympathetic nervous system.
FAU - Luther, Jason A
AU  - Luther JA
AD  - Department of Biology, National Center for Behavioral Genomics, Brandeis 
      University, Waltham, Massachusetts 02454, USA.
FAU - Birren, Susan J
AU  - Birren SJ
LA  - eng
GR  - P30NS45713/NS/NINDS NIH HHS/United States
GR  - R01 HD042716-04/HD/NICHD NIH HHS/United States
GR  - R01 HD042716-05S1/HD/NICHD NIH HHS/United States
GR  - R01 HD042716-02/HD/NICHD NIH HHS/United States
GR  - P30 NS045713/NS/NINDS NIH HHS/United States
GR  - HD042716/HD/NICHD NIH HHS/United States
GR  - R01 HD042716/HD/NICHD NIH HHS/United States
GR  - R01 HD042716-05/HD/NICHD NIH HHS/United States
GR  - R01 HD042716-01A2/HD/NICHD NIH HHS/United States
GR  - R01 HD042716-03/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Ion Channels)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Adrenergic Fibers/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - Ion Channel Gating/physiology
MH  - Ion Channels/*physiology
MH  - Mice
MH  - Neurons/*physiology
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Receptor, Nerve Growth Factor/*physiology
MH  - Receptor, trkA/*physiology
MH  - Signal Transduction/*physiology
PMC - PMC3326291
MID - NIHMS113130
EDAT- 2009/05/01 09:00
MHDA- 2009/06/06 09:00
PMCR- 2009/10/29
CRDT- 2009/05/01 09:00
PHST- 2009/05/01 09:00 [entrez]
PHST- 2009/05/01 09:00 [pubmed]
PHST- 2009/06/06 09:00 [medline]
PHST- 2009/10/29 00:00 [pmc-release]
AID - 29/17/5411 [pii]
AID - 3477317 [pii]
AID - 10.1523/JNEUROSCI.3503-08.2009 [doi]
PST - ppublish
SO  - J Neurosci. 2009 Apr 29;29(17):5411-24. doi: 10.1523/JNEUROSCI.3503-08.2009.