RT Journal Article SR Electronic T1 Fast Sodium Channel Gating Supports Localized and Efficient Axonal Action Potential Initiation JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 10233 OP 10242 DO 10.1523/JNEUROSCI.6335-09.2010 VO 30 IS 30 A1 Schmidt-Hieber, Christoph A1 Bischofberger, Josef YR 2010 UL http://www.jneurosci.org/content/30/30/10233.abstract AB Action potentials (APs) are initiated in the proximal axon of most neurons. In myelinated axons, a 50-times higher sodium channel density in the initial segment compared to the soma may account for this phenomenon. However, little is known about sodium channel density and gating in proximal unmyelinated axons. To study the mechanisms underlying AP initiation in unmyelinated hippocampal mossy fibers of adult mice, we recorded sodium currents in axonal and somatic membrane patches. We demonstrate that sodium channel density in the proximal axon is ∼5 times higher than in the soma. Furthermore, sodium channel activation and inactivation are ∼2 times faster. Modeling revealed that the fast activation localized the initiation site to the proximal axon even upon strong synaptic stimulation, while fast inactivation contributed to energy-efficient membrane charging during APs. Thus, sodium channel gating and density in unmyelinated mossy fiber axons appear to be specialized for robust AP initiation and propagation with minimal current flow.