Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex.

The kinetic behavior of brain Na+ channels was studied in pyramidal cells from rat and cat sensorimotor cortex using either the thin slice preparation or acutely isolated neurons. Single-channel recordings were obtained in the cell-attached and inside-out configuration of the patch-clamp technique. Na+ channels had a conductance of about 16 pS. Patches always contained several Na+ channels, usually 4-12. In both preparations, long depolarizing pulses revealed two distinct patterns of late Na+ channel activity following transient openings. (1) Na+ channels displayed sporadic brief late openings sometimes clustered to "minibursts" of 10-40 msec. These events occurred at a low frequency, yielding open probability (NPo) values below 0.01 (mean = 0.0034). (2) In the second gating mode, an individual Na+ channel in the patch failed to inactivate and produced a burst of openings often lasting to the end of the pulse. This behavior was observed in about 1% of depolarizations. Shifts to the bursting mode were usually confined to a single 400 msec pulse, but rarely occurred during two or more consecutive pulses applied at 2 sec intervals. Sustained bursts did not require preceding transient openings to occur since they were also observed during slow depolarizing voltage ramps. The similar incidence of inactivation failures in cell-attached versus inside-out recordings suggests that the bursting mode is a property of the channel and/or adjacent membrane-bound structures. Calculations indicate that brief late openings and rare sustained bursts suffice to generate a small but significant whole-cell current. Since the Na+ channels mediating early, brief late, and sustained openings were identical in terms of their elementary electrical properties, we propose that the fast and the persistent Na+ currents of cortical pyramidal cells are generated by an electrophysiologically uniform population of Na+ channels that can individually switch between different gating modes.