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Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a.
Neurosci Lett. 2008 Sep 05; 442(1):69-73.NL

Abstract

The voltage-gated sodium channel alpha subunit Na(v)1.6, encoded by the Scn8a gene, accumulates at high density at mature nodes of Ranvier of myelinated axons, replacing the Na(v)1.2 channels found at nodes earlier in development. To investigate this preferential expression of Na(v)1.6 at adult nodes, we examined isoform-specific expression of sodium channels in mice heterozygous for a null mutation in Scn8a. Immunoblots from these +/- mice had 50% of the wild-type level of Na(v)1.6 protein, and their optic-nerve nodes of Ranvier had correspondingly less anti-Na(v)1.6 immunofluorescence. Protein level and nodal immunofluorescence of the Na(v)1.2 alpha subunit increased in Scn8a(+/-) mice, keeping total sodium channel expression approximately constant despite partial loss of Na(v)1.6 channels. The results are consistent with a model in which Na(v)1.6 and Na(v)1.2 compete for binding partners at sites of high channel density, such as nodes of Ranvier. We suggest that Na(v)1.6 channels normally occupy most of the molecular machinery responsible for channel clustering because they have higher binding affinity, and not because they are exclusively recognized by mechanisms for transport and insertion of sodium channels in myelinated axons. The reduced amount of Na(v)1.6 protein in Scn8a(+/-) mice is apparently insufficient to saturate the nodal binding sites, allowing Na(v)1.2 channels to compete more successfully.

Authors+Show Affiliations

Department of Neurobiology and Behavior, State University of New York, Stony Brook, NY 11794-5230, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18601978

Citation

Vega, Ana V., et al. "Reduced Expression of Na(v)1.6 Sodium Channels and Compensation By Na(v)1.2 Channels in Mice Heterozygous for a Null Mutation in Scn8a." Neuroscience Letters, vol. 442, no. 1, 2008, pp. 69-73.
Vega AV, Henry DL, Matthews G. Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a. Neurosci Lett. 2008;442(1):69-73.
Vega, A. V., Henry, D. L., & Matthews, G. (2008). Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a. Neuroscience Letters, 442(1), 69-73. https://doi.org/10.1016/j.neulet.2008.06.065
Vega AV, Henry DL, Matthews G. Reduced Expression of Na(v)1.6 Sodium Channels and Compensation By Na(v)1.2 Channels in Mice Heterozygous for a Null Mutation in Scn8a. Neurosci Lett. 2008 Sep 5;442(1):69-73. PubMed PMID: 18601978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a. AU - Vega,Ana V, AU - Henry,Diane L, AU - Matthews,Gary, Y1 - 2008/06/27/ PY - 2008/05/14/received PY - 2008/06/23/revised PY - 2008/06/24/accepted PY - 2008/7/8/pubmed PY - 2008/10/15/medline PY - 2008/7/8/entrez SP - 69 EP - 73 JF - Neuroscience letters JO - Neurosci Lett VL - 442 IS - 1 N2 - The voltage-gated sodium channel alpha subunit Na(v)1.6, encoded by the Scn8a gene, accumulates at high density at mature nodes of Ranvier of myelinated axons, replacing the Na(v)1.2 channels found at nodes earlier in development. To investigate this preferential expression of Na(v)1.6 at adult nodes, we examined isoform-specific expression of sodium channels in mice heterozygous for a null mutation in Scn8a. Immunoblots from these +/- mice had 50% of the wild-type level of Na(v)1.6 protein, and their optic-nerve nodes of Ranvier had correspondingly less anti-Na(v)1.6 immunofluorescence. Protein level and nodal immunofluorescence of the Na(v)1.2 alpha subunit increased in Scn8a(+/-) mice, keeping total sodium channel expression approximately constant despite partial loss of Na(v)1.6 channels. The results are consistent with a model in which Na(v)1.6 and Na(v)1.2 compete for binding partners at sites of high channel density, such as nodes of Ranvier. We suggest that Na(v)1.6 channels normally occupy most of the molecular machinery responsible for channel clustering because they have higher binding affinity, and not because they are exclusively recognized by mechanisms for transport and insertion of sodium channels in myelinated axons. The reduced amount of Na(v)1.6 protein in Scn8a(+/-) mice is apparently insufficient to saturate the nodal binding sites, allowing Na(v)1.2 channels to compete more successfully. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/18601978/Reduced_expression_of_Na_v_1_6_sodium_channels_and_compensation_by_Na_v_1_2_channels_in_mice_heterozygous_for_a_null_mutation_in_Scn8a_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(08)00918-X DB - PRIME DP - Unbound Medicine ER -