title: Low expression of Kv7/M channels facilitates intrinsic and network bursting in the developing rat hippocampus.
abstract: Early in development, network activity in the hippocampus is characterized by recurrent synchronous bursts, whose cellular correlates are giant depolarizing potentials (GDPs). The propensity for generating GDPs is attributed to GABAergic synaptic transmission being depolarizing and excitatory in neonatal neurons. However, developmental regulation of intrinsic conductances may also influence GDPs generation. A likely candidate is the non-inactivating, low-threshold, muscarinic-sensitive K(+) current (M current; I(m)), which down-regulates intrinsic bursting activity in adult hippocampal pyramidal neurons. Western blot analysis of homogenates of the CA3 hippocampal region showed that expression of the Kv7.2 subunit, one of the constituents of neuronal M channels, is weak in neonatal neurons, and markedly increases after the first postnatal week. Likewise, the density of I(m) was very low in neonatal CA3 pyramidal cells and increased later on. Spontaneously occurring intrinsic bursts in neonatal neurons were longer and more robust, and recurred more regularly, than in juvenile neurons. The I(m) blocker linopirdine only mildly affected intrinsic bursting in neonatal neurons, but strongly facilitated and regularized it in juvenile neurons. We conclude that the low expression of Kv7/M channels and the depolarizing action of GABA early after birth enhance intrinsic bursting and neuronal synchronization leading to generation of GDPs within the hippocampal network.
authors.affiliation: Neuroscience Programme, International School for Advanced Studies, Trieste, Italy.
authors.forename: Victoria F
authors.initials: VF
authors.lastname: Safiulina
authors.forename: Paola
authors.initials: P
authors.lastname: Zacchi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taglialatela
authors.forename: Yoel
authors.initials: Y
authors.lastname: Yaari
authors.forename: Enrico
authors.initials: E
authors.lastname: Cherubini
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002219:Carbamates / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051658:KCNQ2 Potassium Channel / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D009415:Nerve Net / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002219:Carbamates; D007211:Indoles; D051658:KCNQ2 Potassium Channel; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D011725:Pyridines; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; C101866:ezogabine; D005680:gamma-Aminobutyric Acid; C061017:linopirdine
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