title: A novel Na+ channel splice form contributes to the regulation of an androgen-dependent social signal.
abstract: Na(+) channels are often spliced but little is known about the functional consequences of splicing. We have been studying the regulation of Na(+) current inactivation in an electric fish model in which systematic variation in the rate of inactivation of the electric organ Na(+) current shapes the electric organ discharge (EOD), a sexually dimorphic, androgen-sensitive communication signal. Here, we examine the relationship between an Na(+) channel (Na(v)1.4b), which has two splice forms, and the waveform of the EOD. One splice form (Na(v)1.4bL) possesses a novel first exon that encodes a 51 aa N-terminal extension. This is the first report of an Na(+) channel with alternative splicing in the N terminal. This N terminal is present in zebrafish suggesting its general importance in regulating Na(+) currents in teleosts. The extended N terminal significantly speeds fast inactivation, shifts steady-state inactivation, and dramatically enhances recovery from inactivation, essentially fulfilling the functions of a beta subunit. Both splice forms are equally expressed in muscle in electric fish and zebrafish but Na(v)1.4bL is the dominant form in the electric organ implying electric organ-specific transcriptional regulation. Transcript abundance of Na(v)1.4bL in the electric organ is positively correlated with EOD frequency and lowered by androgens. Thus, shaping of the EOD waveform involves the androgenic regulation of a rapidly inactivating splice form of an Na(+) channel. Our results emphasize the role of splicing in the regulation of a vertebrate Na(+) channel and its contribution to a known behavior.
authors.affiliation: Section of Neurobiology and The Institute for Neuroscience, The 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: D017398:Alternative Splicing / Q000235:genetics*; D000728:Androgens / Q000502:physiology*; D000819:Animal Communication; D000818:Animals; D001522:Behavior, Animal; D055592:Biophysical Phenomena; D001703:Biophysics; D004555:Electric Fish; D004557:Electric Organ / Q000166:cytology / Q000378:metabolism; D005260:Female; D005399:Fishes; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D008969:Molecular Sequence Data; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D011392:Proline / Q000235:genetics; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D015222:Sodium Channels / Q000145:classification / Q000235:genetics*; D014981:Xenopus; D015027:Zebrafish
chemical_list: D000728:Androgens; D015222:Sodium Channels; D011392:Proline
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