Voltage-gated sodium channels shape subthreshold EPSPs in layer 5 pyramidal neurons from rat prefrontal cortex

The role of voltage-dependent channels in shaping subthreshold excitatory p ostsynaptic potentials (EPSPs) in neocortical layer 5 pyramidal neurons fro m rat medial prefrontal cortex (PFC) was investigated using patch-clamp rec ordings from visually identified neurons in brain slices. Small-amplitude E PSPs 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-nitroquinoxal ene-2,3-dione, suggesting that they were primarily mediated by AMPA recepto rs. AMPA receptor-mediated EPSPs (AMPA-EPSPs) evoked in the apical dendrite s were markedly enhanced, or increased in peak and duration, at depolarized holding potentials. Enhancement of AMPA-EPSPs was reduced by loading the c ells 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/p roximal apical dendrite. In contrast, blockade of Ca2+ channels by co-appli cation of Cd2+ and Ni2+ to the soma or apical dendrite did not affect the A MPA-EPSPs. Like single EPSPs, EPSP trains were shaped by Na+ but not Ca2+ c hannels. EPSPs simulated by injecting synaptic-like current into proximal/m iddle apical dendrite (simEPSPs) were enhanced at depolarized holding poten tials similarly to AMPA-EPSPs. Extensive blockade of Ca2+ channels by bath application of the Cd2+ and Ni2+ mixture had no effects on simEPSPs, wherea s 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+ current s by high concentrations of 4-AP and TEA revealed a contribution of Ca2+ ch annels to EPSPs that, however, seemed to be dependent on Na+ channel activa tion. 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.