Fine Gating Properties of Channels Responsible for Persistent Sodium Current Generation in Entorhinal Cortex Neurons

The gating properties of channels responsible for the generation of persistent Na(+) current (I (NaP)) in entorhinal cortex layer II principal neurons were investigated by performing cell-attached, patch-clamp experiments in acutely isolated cells. Voltage-gated Na(+)-channel activity was routinely elicited by applying 500-ms depolarizing test pulses positive to −60 mV from a holding potential of −100 mV. The channel activity underlying I (NaP) consisted of prolonged and frequently delayed bursts during which repetitive openings were separated by short closings. The mean duration of openings within bursts was strongly voltage dependent, and increased by e times per every ∼12 mV of depolarization. On the other hand, intraburst closed times showed no major voltage dependence. The mean duration of burst events was also relatively voltage insensitive. The analysis of burst-duration frequency distribution returned two major, relatively voltage-independent time constants of ∼28 and ∼190 ms. The probability of burst openings to occur also appeared largely voltage independent. Because of the above “persistent” Na(+)-channel properties, the voltage dependence of the conductance underlying whole-cell I (NaP) turned out to be largely the consequence of the pronounced voltage dependence of intraburst open times. On the other hand, some kinetic properties of the macroscopic I (NaP), and in particular the fast and intermediate I (NaP)-decay components observed during step depolarizations, were found to largely reflect mean burst duration of the underlying channel openings. A further I (NaP) decay process, namely slow inactivation, was paralleled instead by a progressive increase of interburst closed times during the application of long-lasting (i.e., 20 s) depolarizing pulses. In addition, long-lasting depolarizations also promoted a channel gating modality characterized by shorter burst durations than normally seen using 500-ms test pulses, with a predominant burst-duration time constant of ∼5–6 ms. The above data, therefore, provide a detailed picture of the single-channel bases of I (NaP) voltage-dependent and kinetic properties in entorhinal cortex layer II neurons.