RT Journal Article
SR Electronic
T1 Functional Specialization of the Axon Initial Segment by Isoform-Specific Sodium Channel Targeting
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2306
OP 2313
DO 10.1523/JNEUROSCI.23-06-02306.2003
VO 23
IS 6
A1 Boiko, Tatiana
A1 Van Wart, Audra
A1 Caldwell, John H.
A1 Levinson, S. Rock
A1 Trimmer, James S.
A1 Matthews, Gary
YR 2003
UL http://www.jneurosci.org/content/23/6/2306.abstract
AB Voltage-dependent sodium channels cluster at high density at axon initial segments, where propagating action potentials are thought to arise, and at nodes of Ranvier. Here, we show that the sodium channel Nav1.6 is precisely localized at initial segments of retinal ganglion cells (RGCs), whereas a different isoform, Nav1.2, is found in the neighboring unmyelinated axon. During development, initial segments first expressed Nav1.2, and Nav1.6 appeared later, approximately in parallel with the onset of repetitive RGC firing. In Shiverer mice, Nav1.6 localization at the initial segment was unaffected, although Nav1.6 expression was severely disrupted in the aberrantly myelinated optic nerve. Targeting or retention of Nav1.6 requires molecular interactions that normally occur only at initial segments and nodes of Ranvier. Expression at nodes but not initial segments exhibits an additional requirement for intact myelination. Because of their high density at the initial segment, Nav1.6 channels may be crucial in determining neuronal firing properties.