A Neutral Amino Acid Change in Segment IIS4 Dramatically Alters the Gating Properties of the Voltage-Dependent Sodium Channel
Abstract
Sodium channels encoded by the rat IIA cDNA clone [Auld, V. J., Goldin, A. L., Krafte, D. S., Marshall, J., Dunn, J., Catterall, W. A., Lester, H. A., Davidson, N. & Dunn, R. J. (1988) Neuron 1, 449-461] differ at seven amino acid residues from those encoded by the rat II cDNA [Noda, M., Ikeda, T., Kayano, T., Suzuki, H., Takeshima, H., Kurasaki, M., Takahashi, H. & Numa, S. (1986) Nature (London) 320, 188-192]. When expressed in Xenopus oocytes, rat IIA channels display a current-voltage relationship that is shifted 20-25 mV in the depolarizing direction relative to channels expressed from rat II cDNA or rat brain poly(A)+ mRNA. By modifying each variant residue in rat IIA to the corresponding residue in rat II, we demonstrate that a single Phe → Leu substitution at position 860 in the S4 segment of domain II is sufficient to shift the current-voltage relationship to that observed for channels expressed from rat brain poly(A)+ RNA or rat II cDNA. Rat genomic DNA encodes leucine but not phenylalanine at position 860, indicating that the phenylalanine at this position in rat IIA cDNA likely results from reverse transcriptase error.
Additional Information
© 1990 by National Academy of Sciences Contributed by N. Davidson, September 21, 1989 We thank K. McCormack and co-workers for communication of their observations prior to publication and R. Sarao for technical assistance. This research has been supported by grants from the National Institutes of Health (to N.D., H.A.L., A.L.G., and W.A.C.), by a Klingenstein Foundation grant (to H.A.L.), and by grants from the Multiple Sclerosis Society of Canada and the Medical Research Council of Canada (to R.J.D.). A.L.G. is a Lucille P. Markey Scholar and this work was also supported in part by a grant from the Lucille P. Markey Charitable Trust. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.Attached Files
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Additional details
- PMCID
- PMC53255
- Eprint ID
- 6962
- Resolver ID
- CaltechAUTHORS:AULpnas90
- NIH
- Esther A. and Joseph Klingenstein Fund
- Multiple Sclerosis Society of Canada
- Medical Research Council of Canada
- Lucille P. Markey Charitable Trust
- Created
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2007-01-03Created from EPrint's datestamp field
- Updated
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2019-10-02Created from EPrint's last_modified field