Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster.

Rachel O'Donnell Olson, Zhiqi Liu, Yoshiko Nomura, Weizhong Song, Ke Dong
Author Information
  1. Rachel O'Donnell Olson: Department of Entomology, Neuroscience Program and Genetics Program, Michigan State University, East Lansing, MI 48824, USA.

Abstract

Extensive alternative splicing and RNA editing have been documented for the transcript of DmNa(V) (formerly para), the sole sodium channel gene in Drosophila melanogaster. However, the functional consequences of these post-transcriptional modifications are not well understood. In this study we isolated 64 full-length DmNa(V) cDNA clones from D. melanogaster adults. Based on the usage of 11 alternative exons, 64 clones could be grouped into 29 splice types. When expressed in Xenopus oocytes, 33 DmNa(V) variants generated sodium currents large enough for functional characterization. Among these variants, DmNa(V)5-1 and DmNa(V)7-1 channels activated at the most hyperpolarizing potentials, whereas DmNa(V)1-6 and DmNa(V)19 channels activated at the most depolarizing membrane potentials. We identified an A-to-I editing event in DmNa(V)5-1 that is responsible for its uniquely low-voltage-dependent activation. The wide range of voltage dependence of gating properties exhibited by DmNa(V) variants represents a rich resource for future studies to determine the role of DmNa(V) in regulating sodium channel gating, pharmacology, and neuronal excitability in insects.

References

  1. Neuron. 2000 Nov;28(2):365-8 [PMID: 11144347]
  2. Neuron. 2000 Apr;26(1):13-25 [PMID: 10798388]
  3. Invert Neurosci. 2005 Nov;5(3-4):135-46 [PMID: 16177888]
  4. J Neurosci. 1988 Nov;8(11):4379-93 [PMID: 2460598]
  5. Prog Neurobiol. 2001 Aug;64(5):431-525 [PMID: 11301158]
  6. J Neurosci. 1988 Oct;8(10):3633-43 [PMID: 2848103]
  7. Cell. 2000 Aug 18;102(4):437-49 [PMID: 10966106]
  8. J Neurosci. 1991 Jul;11(7):2135-50 [PMID: 1712379]
  9. Eur J Neurosci. 1999 Apr;11(4):1449-60 [PMID: 10103139]
  10. Genetics. 1995 Sep;141(1):203-14 [PMID: 8536968]
  11. J Biol Chem. 2004 Jul 30;279(31):32554-61 [PMID: 15136570]
  12. Invert Neurosci. 2007 Mar;7(1):17-30 [PMID: 17206406]
  13. J Biol Chem. 1997 Sep 19;272(38):24008-15 [PMID: 9295353]
  14. J Neurophysiol. 1999 Jan;81(1):307-18 [PMID: 9914291]
  15. Invert Neurosci. 2002 Apr;4(3):125-33 [PMID: 12488972]
  16. Biochem Biophys Res Commun. 2006 Jan 20;339(3):939-48 [PMID: 16325765]
  17. J Neurosci. 2002 Jul 1;22(13):5300-9 [PMID: 12097481]
  18. Genome Biol. 2003;4(3):207 [PMID: 12620097]
  19. J Neurosci. 1994 May;14(5 Pt 1):2569-78 [PMID: 8182428]
  20. J Neurosci. 1994 Aug;14(8):4600-12 [PMID: 7519255]
  21. J Gen Physiol. 1997 Aug;110(2):119-33 [PMID: 9236205]
  22. Cell. 1995 Sep 22;82(6):1001-11 [PMID: 7553842]
  23. EXS. 1993;63:366-89 [PMID: 7678530]
  24. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11862-7 [PMID: 15280550]
  25. Cell. 1989 Sep 22;58(6):1143-54 [PMID: 2550145]
  26. Insect Biochem Mol Biol. 2003 Jul;33(7):733-9 [PMID: 12826100]
  27. J Exp Biol. 2000 Jun;203(Pt 11):1633-48 [PMID: 10804154]
  28. J Neurobiol. 1995 May;27(1):113-26 [PMID: 7643071]

Grants

  1. R01 GM057440/NIGMS NIH HHS
  2. R01 GM057440-12/NIGMS NIH HHS

MeSH Term

Alternative Splicing
Animals
DNA, Complementary
Drosophila melanogaster
Ion Channel Gating
Oocytes
RNA Editing
Sequence Analysis, DNA
Sodium Channels
Xenopus

Chemicals

DNA, Complementary
Sodium Channels

Word Cloud

Created with Highcharts 10.0.0DmNaVsodiumvariantschannelmelanogasterfunctionalalternativeeditingDrosophila64clonescharacterization5-1channelsactivatedpotentialsgatingExtensivesplicingRNAdocumentedtranscriptformerlyparasolegeneHoweverconsequencespost-transcriptionalmodificationswellunderstoodstudyisolatedfull-lengthcDNADadultsBasedusage11exonsgrouped29splicetypesexpressedXenopusoocytes33generatedcurrentslargeenoughAmong7-1hyperpolarizingwhereas1-619depolarizingmembraneidentifiedA-to-Ieventresponsibleuniquelylow-voltage-dependentactivationwiderangevoltagedependencepropertiesexhibitedrepresentsrichresourcefuturestudiesdetermineroleregulatingpharmacologyneuronalexcitabilityinsectsMolecularvoltage-gated

Similar Articles

Cited By