PMID- 10051769
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 11
IP  - 2
DP  - 1999 Feb
TI  - Neurotrophic factors modulate hair cells and their potassium currents in chick 
      otocyst explants.
PG  - 682-90
AB  - Neurotrophins, retinoids and their receptors are present in the sensory epithelia 
      of the inner ear during development. We show that these factors modulate the 
      proliferation of hair cells and their K+-currents when the embryonic day 3 (ED 3) 
      presumptive inner ear (i.e. otocyst) is maintained in organ culture. All 
      trans-retinoic acid (RA) increases hair cell differentiation and enhances the 
      acquisition of outward currents, including a delayed rectifier and a fast 
      activating, transient type, voltage-gated potassium current. In contrast, 
      brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) decrease ionic 
      current activity, and the addition of RA with the neurotrophins enhances this 
      inhibitory response in an age-dependent manner. We measured the total number of 
      cells per explant over time to determine precisely when and how these factors 
      inhibit explant growth. We found that high concentrations of BDNF and NT-3 
      administered together, and low concentrations of both neurotrophins combined and 
      administered with RA suppress otocyst cell numbers after 24 h in vitro. This 
      suppressive response is induced by RA and NT-3, not by RA and BDNF. The 
      suppressive or inhibitory influence of NT-3 and RA is the result of NT-3 binding 
      to the low affinity receptor, p75NTR, not the result of RA increasing mRNA levels 
      for the high affinity receptor, trkC. However, trk may act with p75NTR, as 
      disruption of trk signalling alleviates the inhibitory response induced by NT-3 
      and RA. Our data suggest that various combinations and/or concentration gradients 
      of these factors can differentially regulate inner ear development and hair cell 
      excitability.
FAU - Sokolowski, B H
AU  - Sokolowski BH
AD  - University of South Florida, Department of Otolaryngology-Head and Neck Surgery, 
      Tampa 33612, USA.
FAU - Csus, J
AU  - Csus J
FAU - Hafez, O I
AU  - Hafez OI
FAU - Haggerty, H S
AU  - Haggerty HS
LA  - eng
GR  - DC01923/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotrophin 3)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Ciliary Neurotrophic Factor)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkC)
RN  - RWP5GA015D (Potassium)
SB  - IM
EIN - Eur J Neurosci 1999 May;11(5):1847
MH  - Aging/physiology
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Division/drug effects
MH  - Chick Embryo
MH  - Gene Expression/physiology
MH  - Hair Cells, Auditory/chemistry/cytology/*physiology
MH  - Membrane Potentials/drug effects/physiology
MH  - Nerve Growth Factors/*pharmacology
MH  - Neurotrophin 3
MH  - Organ Culture Techniques
MH  - Patch-Clamp Techniques
MH  - Potassium/*metabolism
MH  - RNA, Messenger/analysis
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
MH  - Receptor, Ciliary Neurotrophic Factor
MH  - Receptor, Nerve Growth Factor
MH  - Receptor, trkC
MH  - Receptors, Nerve Growth Factor/genetics/metabolism/physiology
MH  - Tretinoin/metabolism/pharmacology
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - 10.1046/j.1460-9568.1999.00469.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 1999 Feb;11(2):682-90. doi: 10.1046/j.1460-9568.1999.00469.x.