Functional specialization of the axon initial segment by isoform-specific sodium channel targeting

被引:0
|
作者
Boiko, T
Van Wart, A
Caldwell, JH
Levinson, SR
Trimmer, JS
Matthews, G
机构
[1] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA
[3] Univ Colorado, Sch Med, Dept Cellular & Struct Biol, Denver, CO 80262 USA
[4] Univ Colorado, Sch Med, Dept Physiol, Denver, CO 80262 USA
来源
JOURNAL OF NEUROSCIENCE | 2003年 / 23卷 / 06期
关键词
sodium channels; initial segment; action potential initiation; retina; retinal ganglion cell; development; optic nerve;
D O I
暂无
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 Na(v)1.6 is precisely localized at initial segments of retinal ganglion cells (RGCs), whereas a different isoform, Na(v)1.2, is found in the neighboring unmyelinated axon. During development, initial segments first expressed Na(v)1.2, and Na(v)1.6 appeared later, approximately in parallel with the onset of repetitive RGC firing. In Shiverer mice, Na(v)1.6 localization at the initial segment was unaffected, although Na(v)1.6 expression was severely disrupted in the aberrantly myelinated optic nerve. Targeting or retention of Na(v)1.6 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, Na(v)1.6 channels may be crucial in determining neuronal firing properties.
引用
收藏
页码:2306 / 2313
页数:8
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