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  1. Article: Regional differences in nerve terminal Na⁺ channel subtype expression and Na⁺ channel-dependent glutamate and GABA release in rat CNS

    Westphalen, Robert I / Yu, Jieying / Krivitski, Margarita / Jih, Ting-Yu / Hemmings Jr, Hugh C

    Journal of neurochemistry. 2010 June, v. 113, no. 6

    2010  

    Abstract: J. Neurochem. (2010) 113, 1611-1620. We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Nav) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific ... ...

    Abstract J. Neurochem. (2010) 113, 1611-1620. We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Nav) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Nav coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [³H]glutamate and [¹⁴C]GABA release to the specific Nav blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Nav subtypes was measured by immunoblotting using subtype-specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release varied between CNS regions. However, the efficacies of TTX for inhibition of 4AP-evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Nav subtypes as well as of specific subtypes varied considerably between CNS regions. The region-specific potencies of TTX for inhibition of 4AP-evoked glutamate release correlated with greater relative expression of total nerve terminal Nav and Nav1.2. Nerve terminal-specific differences in the expression of specific Nav subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.
    Keywords sodium channels ; tetrodotoxin
    Language English
    Dates of publication 2010-06
    Size p. 1611-1620.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2010.06722.x
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel-dependent glutamate and GABA release in rat CNS.

    Westphalen, Robert I / Yu, Jieying / Krivitski, Margarita / Jih, Ting-Yu / Hemmings, Hugh C

    Journal of neurochemistry

    2010  Volume 113, Issue 6, Page(s) 1611–1620

    Abstract: We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Na(v)) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Na(v) coupling to ... ...

    Abstract We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Na(v)) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Na(v) coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [(3)H]glutamate and [(14)C]GABA release to the specific Na(v) blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Na(v) subtypes was measured by immunoblotting using subtype-specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release varied between CNS regions. However, the efficacies of TTX for inhibition of 4AP-evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Na(v) subtypes as well as of specific subtypes varied considerably between CNS regions. The region-specific potencies of TTX for inhibition of 4AP-evoked glutamate release correlated with greater relative expression of total nerve terminal Na(v) and Na(v)1.2. Nerve terminal-specific differences in the expression of specific Na(v) subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.
    MeSH term(s) 4-Aminopyridine/pharmacology ; Aniline Compounds/pharmacology ; Animals ; Central Nervous System/anatomy & histology ; Central Nervous System/metabolism ; Dose-Response Relationship, Drug ; Drug Interactions ; Furans/pharmacology ; Gene Expression/physiology ; Glutamic Acid/metabolism ; Male ; Potassium Channel Blockers/pharmacology ; Presynaptic Terminals/drug effects ; Presynaptic Terminals/metabolism ; Protein Subunits/metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium Channel Blockers/pharmacology ; Sodium Channels/genetics ; Sodium Channels/metabolism ; Tetrodotoxin/pharmacology ; Veratridine/pharmacology ; gamma-Aminobutyric Acid/metabolism
    Chemical Substances A 803467 ; Aniline Compounds ; Furans ; Potassium Channel Blockers ; Protein Subunits ; Sodium Channel Blockers ; Sodium Channels ; Glutamic Acid (3KX376GY7L) ; Tetrodotoxin (4368-28-9) ; gamma-Aminobutyric Acid (56-12-2) ; Veratridine (71-62-5) ; 4-Aminopyridine (BH3B64OKL9)
    Language English
    Publishing date 2010-03-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2010.06722.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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