NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
A Novel Tetrodotoxin-sensitive, Voltage-gated Sodium Channel Expressed in Rat and Human Dorsal Root Ganglia*

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Dorsal root ganglion neurons express a wide repertoire of sodium channels with different properties. Here, we report the cloning from rat, dorsal root ganglia (DRG), cellular expression, and functional analysis of a novel tetrodotoxin-sensitive peripheral sodium channel (PN), PN1. PN1 mRNA is expressed in many different tissues. Within the rat DRG, both the mRNA and PN1-like immunoreactivity are present in small and large neurons. The abundance of sodium channel mRNAs in rat DRG is rBI > PN1 ≥ PN3 >>> rBIII by quantitative reverse transcription-polymerase chain reaction analysis. Data from reverse transcription-polymerase chain reaction and sequence analyses of human DRG and other human tissues suggest that rat PN1 is an ortholog of the human neuroendocrine channel. In Xenopus oocytes, PN1 exhibits kinetics that are similar to rBIIa sodium currents and is inhibited by tetrodotoxin with an IC50 of 4.3 ± 0.92 nm. Unlike rBIIa, the inactivation kinetics of PN1 are not accelerated by the coexpression of the β-subunits.

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*

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Present address: Dept. of Physiology, 302 Hamilton Hall, Ohio State University, 1645 Neil Ave., Columbus, OH 43210.

Present address: Alza Corp., 950 Page Mill Rd., Palo Alto, CA 10950.

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Present address: Calydon, 1014 Hamilton Ct., Menlo Park, CA 94025.

1

The abbreviations used are:

    DRG

    dorsal root ganglia

    PN

    peripheral sodium channel

    TTX

    tetrodotoxin

    hNE

    human neuroendocrine channel

    RT

    reverse transcription

    PCR

    polymerase chain reaction

    QRT-PCR

    quantitative RT-PCR

    bp

    base pair

    PBS

    phosphate-buffered saline

    TEVC

    two-electrode voltage clamp

    kb

    kilobase(s)

© 1997 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.