PMID- 22796476
OWN - NLM
STAT- MEDLINE
DCOM- 20130110
LR  - 20120810
IS  - 1878-5891 (Electronic)
IS  - 0378-5955 (Linking)
VI  - 291
IP  - 1-2
DP  - 2012 Sep
TI  - Combined application of brain-derived neurotrophic factor and neurotrophin-3 and 
      its impact on spiral ganglion neuron firing properties and 
      hyperpolarization-activated currents.
PG  - 1-14
LID - 10.1016/j.heares.2012.07.002 [doi]
AB  - Neurotrophins provide an effective tool for the rescue and regeneration of spiral 
      ganglion neurons (SGNs) following sensorineural hearing loss. However, these 
      nerve growth factors are also potent modulators of ion channel activity and 
      expression, and in the peripheral auditory system brain-derived neurotrophic 
      factor (BDNF) and neurotrophin-3 (NT3) have previously been shown to alter the 
      firing properties of auditory neurons and differentially regulate the expression 
      of some potassium channels in vitro. In this study we examined the activity of 
      the hyperpolarization-mediated mixed-cation current (I(h)) in early post-natal 
      cultured rat SGNs following exposure to combined BDNF and NT3. Whole-cell 
      patch-clamp recordings made after 1 or 2 days in vitro revealed no change in the 
      firing adaptation of neurons in the presence of BDNF and NT3. Resting membrane 
      potentials were also maintained, but spike latency and firing threshold was 
      subject to regulation by both neurotrophins and time in vitro. Current clamp 
      recordings revealed an activity profile consistent with activation of the 
      hyperpolarization-activated current. Rapid membrane hyperpolarization was 
      followed by a voltage- and time-dependent depolarizing voltage sag. In voltage 
      clamp, membrane hyperpolarization evoked a slowly-activating inward current that 
      was reversibly blocked with cesium and inhibited by ZD7288. The amplitude and 
      current density of I(h) was significantly larger in BDNF and NT3 supplemented 
      cultures, but this did not translate to a significant alteration in voltage sag 
      magnitude. Neurotrophins provided at 50 ng/ml produced a hyperpolarizing shift in 
      the voltage-dependence and slower time course of I(h) activation compared to SGNs 
      in control groups or cultured with 10 ng/ml BDNF and NT3. Our results indicate 
      that combined BDNF and NT3 increase the activity of hyperpolarization-activated 
      currents and that the voltage-dependence and activation kinetics of I(h) in SGNs 
      are sensitive to changes in neurotrophin concentration. In addition, BDNF and NT3 
      applied together induce a decrease in firing threshold, but does not generate a 
      shift in firing adaptation.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Needham, Karina
AU  - Needham K
AD  - Department of Otolaryngology, University of Melbourne, Royal Victorian Eye & Ear 
      Hospital, Level 2, 32 Gisborne St., East Melbourne, Victoria 3002, Australia. 
      k.needham@unimelb.edu.au
FAU - Nayagam, Bryony A
AU  - Nayagam BA
FAU - Minter, Ricki L
AU  - Minter RL
FAU - O'Leary, Stephen J
AU  - O'Leary SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120714
PL  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotrophin 3)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage
MH  - Cells, Cultured
MH  - Drug Interactions
MH  - Electrophysiological Phenomena
MH  - Hearing Loss, Sensorineural/drug therapy/physiopathology
MH  - Membrane Potentials/drug effects
MH  - Models, Neurological
MH  - Neurons, Afferent/drug effects/physiology
MH  - Neurotrophin 3/*administration & dosage
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Spiral Ganglion/*drug effects/*physiology
EDAT- 2012/07/17 06:00
MHDA- 2013/01/11 06:00
CRDT- 2012/07/17 06:00
PHST- 2012/02/01 00:00 [received]
PHST- 2012/06/29 00:00 [revised]
PHST- 2012/07/03 00:00 [accepted]
PHST- 2012/07/17 06:00 [entrez]
PHST- 2012/07/17 06:00 [pubmed]
PHST- 2013/01/11 06:00 [medline]
AID - S0378-5955(12)00178-5 [pii]
AID - 10.1016/j.heares.2012.07.002 [doi]
PST - ppublish
SO  - Hear Res. 2012 Sep;291(1-2):1-14. doi: 10.1016/j.heares.2012.07.002. Epub 2012 
      Jul 14.