High conductance sustained single-channel activity responsible for the low-threshold persistent Na+ current in entorhinal cortex neurons

Stellate cells from entorhinal cortex (EC) layer II express both a transien t Na+ current (I-Na) and a low-threshold persistent Na+ current (I-NaP) tha t helps to generate intrinsic theta-like oscillatory activity. We have used single-channel patch-clamp recording to investigate the Na+ channels respo nsible for I-NaP in EC stellate cells. Macropatch (more than six channels) recordings showed high levels of transient Na+ channel activity, consisting of brief openings near the beginning of depolarizing pulses, and lower lev els of persistent Na+ channel activity, characterized by prolonged openings throughout 500 msec long depolarizations. The persistent activity contribu ted a noninactivating component to averaged macropatch recordings that was comparable with whole-cell I-NaP in both voltage dependence of activation ( 10 mV negative to the transient current) and amplitude (1% of the transient current at -20 mV). In 14 oligochannel (less than six channels) patches, t he ratio of transient to persistent channel activity varied from patch to p atch, with 10 patches exhibiting exclusively transient openings and one pat ch showing exclusively persistent openings. In two patches containing only a single persistent channel, prolonged openings were observed in >50% of te st depolarizations. Moreover, persistent openings had a significantly highe r single-channel conductance (19.7 pS) than transient openings (15.6 pS). W e conclude that this stable high-conductance persistent channel activity is responsible for I-NaP in EC stellate cells. This persistent channel behavi or is more enduring and has a higher conductance than the infrequent and sh ort-lived transitions to persistent gating modes that have been described p reviously in brain neurons.