A supercritical density of Na(+) channels ensures fast signaling in GABAergic interneuron axons.

Fast-spiking, parvalbumin-expressing GABAergic interneurons, a large proportion of which are basket cells (BCs), have a key role in feedforward and feedback inhibition, gamma oscillations and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. We examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ~20 μm from the soma and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na(+) conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block revealed that low axonal Na(+) conductance density was sufficient for reliability, but high Na(+) density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na(+) channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing.