title: Individual variation and hormonal modulation of a sodium channel beta subunit in the electric organ correlate with variation in a social signal.
abstract: The sodium channel beta1 subunit affects sodium channel gating and surface density, but little is known about the factors that regulate beta1 expression or its participation in the fine control of cellular excitability. In this study we examined whether graded expression of the beta1 subunit contributes to the gradient in sodium current inactivation, which is tightly controlled and directly related to a social behavior, the electric organ discharge (EOD), in a weakly electric fish Sternopygus macrurus. We found the mRNA and protein levels of beta1 in the electric organ both correlate with EOD frequency. We identified a novel mRNA splice form of this gene and found the splicing preference for this novel splice form also correlates with EOD frequency. Androgen implants lowered EOD frequency and decreased the beta1 mRNA level but did not affect splicing. Coexpression of each splice form in Xenopus oocytes with either the human muscle sodium channel gene, hNav1.4, or a Sternopygus ortholog, smNav1.4b, sped the rate of inactivation of the sodium current and shifted the steady-state inactivation toward less negative membrane potentials. The translational product of the novel mRNA splice form lacks a previously identified important tyrosine residue but still functions normally. The properties of the fish alpha and coexpressed beta1 subunits in the oocyte replicate those of the electric organ's endogenous sodium current. These data highlight the role of ion channel beta subunits in regulating cellular excitability.
authors.affiliation: Section of Neurobiology and the Institute of Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Wu
authors.forename: Harold H
authors.initials: HH
authors.lastname: Zakon
mesh_terms: D000200:Action Potentials / Q000235:genetics; D017398:Alternative Splicing / Q000502:physiology; D000819:Animal Communication; D000818:Animals; D004555:Electric Fish / Q000502:physiology*; D004557:Electric Organ / Q000502:physiology*; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009865:Oocytes / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D014981:Xenopus
chemical_list: D006728:Hormones; D009124:Muscle Proteins; D062553:NAV1.4 Voltage-Gated Sodium Channel; D020033:Protein Isoforms; D021122:Protein Subunits; D012333:RNA, Messenger; C106251:SCN4A protein, human; D015222:Sodium Channels; D012964:Sodium