Function of specific K+ channels in sustained high-frequency firing of fast-spiking neocortical interneurons

Function of specific K+ channels in sustained high-frequency firing of fast -spiking neocortical interneurons. J. Neurophysiol. 82: 2476-2489, 1999. Fa st-spiking GABAergic interneurons of the neocortex and hippocampus fire hig h-frequency trains of brief action potentials with little spike-frequency a daptation. How these striking properties arise is unclear, although recent evidence suggests K+ channels containing Kv3.1-Kv3.2 proteins play an impor tant role. We investigated the role of these channels in the firing propert ies of fast-spiking neocortical interneurons from mouse somatosensory corte x using a pharmacological and modeling approach. Low tetraethylammonium (TE A) concentrations (less than or equal to 1 mM), which block only a few know n K+ channels including Kv3.1-Kv3.2, profoundly impaired action potential r epolarization and high-frequency firing. Analysis of the spike trains evoke d by steady depolarization revealed that, although TEA had little effect on the initial firing rate, it strongly reduced firing frequency later in the trains. These effects appeared to be specific to Kv3.1 and Kv3.2 channels, because blockade of dendrotoxin-sensitive Kv1 channels and BK Ca2+-activat ed K+ channels, which also have high TEA sensitivity, produced opposite or no effects. Voltage-clamp experiments confirmed the presence of a Kv3.1-Kv3 .2-like current in fast-spiking neurons, but not in other interneurons. Ana lysis of spike shape changes during the spike trains suggested that Naf cha nnel inactivation plays a significant role in the firing-rate slowdown prod uced by TEA, a conclusion that was supported by computer simulations. These findings indicate that the unique properties of Kv3.1-Kv3.2 channels enabl e sustained high-frequency firing by facilitating the recovery of Na+ chann el inactivation and by minimizing the duration of the afterhyperpolarizatio n in neocortical interneurons.