title: Transforming growth factor-alpha changes firing properties of developing neocortical GABAergic neurons by down-regulation of voltage-gated potassium currents.
abstract: 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.
authors: Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata 951-8585, Japan. hnamba@bri.niigata-u.ac.jp
authors: H
authors: H
authors: Namba
authors: N
authors: N
authors: Takei
authors: H
authors: H
authors: Nawa
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019579:Neocortex / Q000166:cytology*; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011930:Reaction Time; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051669:Shab Potassium Channels; D013779:Tetrodotoxin / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D016211:Transforming Growth Factor alpha; D002104:Cadmium; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D011188:Potassium