title: Voltage-gated sodium channels shape subthreshold EPSPs in layer 5 pyramidal neurons from rat prefrontal cortex.
abstract: The role of voltage-dependent channels in shaping subthreshold excitatory postsynaptic potentials (EPSPs) in neocortical layer 5 pyramidal neurons from rat medial prefrontal cortex (PFC) was investigated using patch-clamp recordings from visually identified neurons in brain slices. Small-amplitude EPSPs evoked by stimulation of superficial layers were not affected by the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonopentanoic acid but were abolished by the AMPA receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione, suggesting that they were primarily mediated by AMPA receptors. AMPA receptor-mediated EPSPs (AMPA-EPSPs) evoked in the apical dendrites were markedly enhanced, or increased in peak and duration, at depolarized holding potentials. Enhancement of AMPA-EPSPs was reduced by loading the cells with lidocaine N-ethylbromide (QX-314) and by local application of the Na(+) channel blocker tetrodotoxin (TTX) to the soma but not to the middle/proximal apical dendrite. In contrast, blockade of Ca(2+) channels by co-application of Cd(2+) and Ni(2+) to the soma or apical dendrite did not affect the AMPA-EPSPs. Like single EPSPs, EPSP trains were shaped by Na(+) but not Ca(2+) channels. EPSPs simulated by injecting synaptic-like current into proximal/middle apical dendrite (simEPSPs) were enhanced at depolarized holding potentials similarly to AMPA-EPSPs. Extensive blockade of Ca(2+) channels by bath application of the Cd(2+) and Ni(2+) mixture had no effects on simEPSPs, whereas bath-applied TTX removed the depolarization-dependent EPSP amplification. Inhibition of K(+) currents by 4-aminopyridine (4-AP) and TEA increased the TTX-sensitive EPSP amplification. Moreover, strong inhibition of K(+) currents by high concentrations of 4-AP and TEA revealed a contribution of Ca(2+) channels to EPSPs that, however, seemed to be dependent on Na(+) channel activation. Our results indicate that in layer 5 pyramidal neurons from PFC, Na(+), and K(+) voltage-gated channels shape EPSPs within the voltage range that is subthreshold for somatic action potentials.
authors.affiliation: Department of Neuroscience and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. burgos@bns.pitt.edu
authors.forename: G
authors.initials: G
authors.lastname: González-Burgos
authors.forename: G
authors.initials: G
authors.lastname: Barrionuevo
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009532:Nickel / Q000494:pharmacology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D015222:Sodium Channels; D002104:Cadmium; C012647:QX-314; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D009532:Nickel; D008012:Lidocaine; D015761:4-Aminopyridine