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The Journal of Neuroscience, March 15, 2003, 23(6):2306
Functional Specialization of the Axon Initial Segment by
Isoform-Specific Sodium Channel Targeting
Tatiana
Boiko1,
Audra
Van Wart1,
John H.
Caldwell3,
S. Rock
Levinson4,
James S.
Trimmer2, and
Gary
Matthews1
Departments of 1 Neurobiology and Behavior and
2 Biochemistry and Cell Biology, State University of New
York, Stony Brook, New York 11794, and Departments of
3 Cellular and Structural Biology and
4 Physiology, University of Colorado Medical School,
Denver, Colorado 80262
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.
Key words:
sodium channels; initial segment; action potential
initiation; retina; retinal ganglion cell; development; optic nerve
Copyright © 2003 Society for Neuroscience 0270-6474/03/2362306-08$05.00/0
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