The exact site of initiation and shape of action potentials vary among different neuronal
types. The reason for this variability is largely unknown, but the subunit composition,
density and distribution of voltage-gated sodium (Nav) and potassium (Kv) channels
within the axon initial segment (AIS) are likely to play a key role. Here, we asked
how heterogeneous are the density and distribution of Nav and Kv channels within the
AISs of a variety of excitatory and inhibitory neurons. Most of the studied cell types
expressed a high density of Nav1.6, Kv1.1, and Kv1.2 subunits in their AIS, but the
Nav1.1 subunit could only be detected in GABAergic interneurons. A proximo-distal
gradient in the density of these subunits was observed within the AIS of certain nerve
cells but not in others. For example, a gradual increase of the Nav1.6 subunit was
observed in cortical layer 2/3 and hippocampal CA1 pyramidal cell (PC) AISs, whereas
its density was rather uniform in layer 5 PC AISs. The Nav1.1 subunit was distributed
evenly along the AIS of short-axon cells of the main olfactory bulb but was restricted
to the proximal part of the AIS in cortical and cerebellar interneurons. Our results
reveal a cell type-dependent expression of sodium and potassium channel subunits with
varying densities along the proximo-distal axis of the AISs. This precise arrangement
is likely to contribute to the diversity of firing properties observed among central
neurons.
