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Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.

Publication ,  Journal Article
Tan, J; Liu, Z; Nomura, Y; Goldin, AL; Dong, K
Published in: The Journal of neuroscience : the official journal of the Society for Neuroscience
July 2002

Alternative splicing is a major mechanism by which potassium and calcium channels increase functional diversity in animals. Extensive alternative splicing of the para sodium channel gene and developmental regulation of alternative splicing have been reported in Drosophila species. Alternative splicing has also been observed for several mammalian voltage-gated sodium channel genes. However, the functional significance of alternative splicing of sodium channels has not been demonstrated. In this study, we identified three mutually exclusive alternative exons encoding part of segments 3 and 4 of domain III in the German cockroach sodium channel gene, para(CSMA). The splice site is conserved in the mouse, fish, and human Na(v)1.6 sodium channel genes, suggesting an ancient origin. One of the alternative exons possesses a stop codon, which would generate a truncated protein with only the first two domains. The splicing variant containing the stop codon is detected only in the PNS, whereas the other two full-size variants were detected in both the PNS and CNS. When expressed in Xenopus oocytes, the two splicing variants produced robust sodium currents, but with different gating properties, whereas the splicing variant with the stop codon did not produce any detectable sodium current. Furthermore, these two functional splicing variants exhibited a striking difference in sensitivity to a pyrethroid insecticide, deltamethrin. Exon swapping partially reversed the channel sensitivity to deltamethrin. Our results therefore provide the first evidence that alternative splicing of a sodium channel gene produces pharmacologically distinct channels.

Duke Scholars

Published In

The Journal of neuroscience : the official journal of the Society for Neuroscience

EISSN

1529-2401

ISSN

0270-6474

Publication Date

July 2002

Volume

22

Issue

13

Start / End Page

5300 / 5309

Related Subject Headings

  • Xenopus
  • Tissue Distribution
  • Sodium Channels
  • Sodium Channel Blockers
  • Sequence Alignment
  • RNA, Messenger
  • Pyrethrins
  • Nitriles
  • Neurology & Neurosurgery
  • Molecular Sequence Data
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tan, J., Liu, Z., Nomura, Y., Goldin, A. L., & Dong, K. (2002). Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 22(13), 5300–5309.
Tan, Jianguo, Zhiqi Liu, Yoshiko Nomura, Alan L. Goldin, and Ke Dong. “Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 22, no. 13 (July 2002): 5300–5309.
Tan J, Liu Z, Nomura Y, Goldin AL, Dong K. Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2002 Jul;22(13):5300–9.
Tan, Jianguo, et al. “Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, vol. 22, no. 13, July 2002, pp. 5300–09.
Tan J, Liu Z, Nomura Y, Goldin AL, Dong K. Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2002 Jul;22(13):5300–5309.

Published In

The Journal of neuroscience : the official journal of the Society for Neuroscience

EISSN

1529-2401

ISSN

0270-6474

Publication Date

July 2002

Volume

22

Issue

13

Start / End Page

5300 / 5309

Related Subject Headings

  • Xenopus
  • Tissue Distribution
  • Sodium Channels
  • Sodium Channel Blockers
  • Sequence Alignment
  • RNA, Messenger
  • Pyrethrins
  • Nitriles
  • Neurology & Neurosurgery
  • Molecular Sequence Data