Nature Neuroscience published a cover story research article entitled "Distinct contributions of Na_v1.6 and Na_v1.2 in action potential initiation and backpropagation" on July 26, 2009. This study was carried out by Wenqin Hu and others from the laboratory of Dr. Yousheng Shu at the Institute of Neuroscience, and was highlighted in a News and Views article authored by Dulla and Huguenard.  

This study tried to answer a fundamental question in the field of neuroscience: what is the mechanism for action potential initiation and propagation? A persisting puzzle in neuroscience has been why action potentials prefer to initiate at the distal end rather than the proximal region of the axon initial segment (AIS) when both locations have similarly high density of Na⁺ channels. With quantitative immunostaining methods, the authors found that high-threshold Na_v1.2 channels preferentially accumulate at the proximal AIS, whereas low-threshold Na_v1.6 channels accumulate at the distal end of the AIS, corresponding to the action potential initiation zone. Electrophysiological and modeling studies revealed that the distal-AIS Nav1.6 promotes action potential initiation, whereas the proximal-AIS Nav1.2 promotes action potential propagation to the soma and dendrites. Therefore, the two Na⁺ channel subtypes serve distinct functions in action potential initiation and backpropagation.