Neuronal activity and TrkB ligands influence Kv3.1b and Kv3.2 expression in developing cortical interneurons.
Among the GABAergic neocortical interneurons, fast-spiking (FS) basket and chandelier cells are essential mediators for feed-forward inhibition, network synchrony and oscillations. The FS properties are in part mediated by the voltage-gated potassium channels Kv3.1b/3.2 which allow the fast repolarization of the membrane necessary for firing non-adapting action potentials at high frequencies. It has been recently reported that the FS phenotype fails to mature in BDNF knockout mice suggesting a role for neurotrophins. We now describe the role of neuronal activity and neurotrophins for Kv3.1b/3.2 expression using organotypic cultures of rat visual cortex as model system. Chronic activity deprivation from 2 days in vitro (DIV) prevented the postnatal developmental increase of Kv3.2, but not Kv3.1b mRNA expression. However, chronic activity deprivation failed to alter Kv3.1b and marginally delayed Kv3.2 protein expression. Activity deprivation by glutamate receptor blockade from 10 to 20 DIV reduced both mRNAs, whereas deprivation with tetrodotoxin (TTX) reduced both mRNAs and the Kv3.2 protein. Thalamic and cortical afferents in cocultures failed to alter the expression. BDNF and NT4 supplemented from 2 DIV onwards increased the expression of Kv3.1b, but not Kv3.2 mRNA in young cultures. Only NT4 increased the expression of both mRNAs later in development. Kv3 protein levels were not changed by exogenous tropomyosin-related kinase B (TrkB) ligands, but the levels decreased upon inhibiting the MAPK signaling suggesting a role for endogenous factors and in particular MEK2 signaling for translation. The results show that Kv3.1b/3.2 expression is differentially controlled by neuronal activity and neurotrophic factors.
Grabert
J
J
AG Entwicklungsneurobiologie, Fakultät für Biologie und Biotechnologie ND 6/72, Ruhr-Universität, 44780 Bochum, Germany.
Wahle
P
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020813:Receptor, trkB / Q000502:physiology*; D051670:Shaw Potassium Channels / Q000235:genetics / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013788:Thalamus / Q000166:cytology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology*
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; C098254:Kcnc1 protein, rat; C489595:Kcnc2 protein, rat; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051670:Shaw Potassium Channels; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C056639:2-amino-5-phosphopentanoic acid; D020813:Receptor, trkB; D014633:Valine; D008274:Magnesium; C073922:neurotrophin 4