PMID- 14622907
OWN - NLM
STAT- MEDLINE
DCOM- 20040217
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 122
IP  - 3
DP  - 2003
TI  - Transforming growth factor-alpha changes firing properties of developing 
      neocortical GABAergic neurons by down-regulation of voltage-gated potassium 
      currents.
PG  - 637-46
AB  - Transforming growth factor-alpha (TGFalpha), a member of the epidermal growth 
      factor family, has neurotrophic actions on postmitotic neurons. We examined the 
      chronic effects of TGFalpha on the electrophysiological properties of one type of 
      GABAergic neuron, identified by its bipolar morphology, in neocortical primary 
      culture. Approximately 85% of the bipolar neurons were GABA-immunoreactive. In 
      response to depolarizing current injection, the bipolar neurons usually showed 
      tonic firing of action potential under control conditions. After treatment with 
      TGFalpha (20 ng/ml) for 2 days, these neurons failed to generate trains of action 
      potentials. Furthermore, the treatment altered the action potential waveforms of 
      the bipolar neurons, including the duration and amplitude of the fast 
      after-hyperpolarization, which implies a reduction in voltage-gated potassium 
      currents. In contrast, TGFalpha did not affect the firing properties of 
      pyramidal-shaped non-GABAergic neurons. Voltage-clamp recordings from the bipolar 
      neurons indicated that chronic treatment with TGFalpha markedly decreased the 
      current densities of slow delayed rectifier (IK) and transient voltage-gated 
      potassium currents, whereas the treatment had no effect on voltage-gated sodium 
      current and fast delayed rectifier potassium current densities. Reverse 
      transcription-polymerase chain reaction analysis of potassium channel mRNA in the 
      bipolar neurons revealed that the reduction in the IK current density was caused 
      by Kv2.2 mRNA down-regulation. Thus, chronic treatment with TGFalpha 
      down-regulated slow delayed rectifier and transient voltage-gated potassium 
      currents, and in parallel, suppressed repetitive generation of action potentials 
      in the cortical GABAergic neurons.
FAU - Namba, H
AU  - Namba H
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, 1-757 Asahimachi, Niigata 951-8585, Japan. hnamba@bri.niigata-u.ac.jp
FAU - Takei, N
AU  - Takei N
FAU - Nawa, H
AU  - Nawa H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Anesthetics, Local)
RN  - 0 (Delayed Rectifier Potassium Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (RNA, Messenger)
RN  - 0 (Shab Potassium Channels)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 00BH33GNGH (Cadmium)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - BH3B64OKL9 (4-Aminopyridine)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - 4-Aminopyridine/pharmacology
MH  - Action Potentials/drug effects
MH  - Anesthetics, Local/pharmacology
MH  - Animals
MH  - Cadmium/pharmacology
MH  - Delayed Rectifier Potassium Channels
MH  - Dose-Response Relationship, Radiation
MH  - Drug Interactions
MH  - Electric Stimulation
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Neocortex/*cytology
MH  - Neurons/classification/*drug effects/physiology
MH  - Organ Culture Techniques
MH  - Potassium/pharmacology
MH  - Potassium Channel Blockers/pharmacology
MH  - Potassium Channels/drug effects/genetics/*metabolism/physiology
MH  - *Potassium Channels, Voltage-Gated
MH  - Pyramidal Cells/drug effects/physiology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Reaction Time
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Shab Potassium Channels
MH  - Tetrodotoxin/pharmacology
MH  - Transforming Growth Factor alpha/*pharmacology
MH  - gamma-Aminobutyric Acid/*metabolism
EDAT- 2003/11/19 05:00
MHDA- 2004/02/18 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2004/02/18 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - S030645220300647X [pii]
AID - 10.1016/j.neuroscience.2003.08.013 [doi]
PST - ppublish
SO  - Neuroscience. 2003;122(3):637-46. doi: 10.1016/j.neuroscience.2003.08.013.