The Drosophila para sodium channel α subunit was expressed in Xenopus oocytes alone and in combination with tipE, a putative Drosophila sodium channel accessory subunit. Coexpression of tipE with para results in elevated levels of sodium currents and accelerated current decay. Para/TipE sodium channels have biophysical and pharmacological properties similar to those of native channels. However, the pharmacology of these channels differs from that of vertebrate sodium channels: (a) toxin II from Anemonia sulcata, which slows inactivation, binds to Para and some mammalian sodium channels with similar affinity (Kd ≅ 10 nM), but this toxin causes a 100-fold greater decrease in the rate of inactivation of Para/TipE than of mammalian channels; (b) Para sodium channels are >10-fold more sensitive to block by tetrodotoxin; and (c) modification by the pyrethroid insecticide permethrin is >100-fold more potent for Para than for rat brain type IIA sodium channels. Our results suggest that the selective toxicity of pyrethroid insecticides is due at least in part to the greater affinity of pyrethroids for insect sodium channels than for mammalian sodium channels.
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1 August 1997
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August 01 1997
Functional Expression of Drosophila para Sodium Channels : Modulation by the Membrane Protein TipE and Toxin Pharmacology
Jeffrey W. Warmke,
Jeffrey W. Warmke
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Robert A.G. Reenan,
Robert A.G. Reenan
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Peiyi Wang,
Peiyi Wang
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Su Qian,
Su Qian
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Joseph P. Arena,
Joseph P. Arena
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Jixin Wang,
Jixin Wang
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Denise Wunderler,
Denise Wunderler
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Ken Liu,
Ken Liu
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Gregory J. Kaczorowski,
Gregory J. Kaczorowski
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Lex H.T. Van der Ploeg,
Lex H.T. Van der Ploeg
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Barry Ganetzky,
Barry Ganetzky
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Charles J. Cohen
Charles J. Cohen
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
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Jeffrey W. Warmke
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Robert A.G. Reenan
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Peiyi Wang
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Su Qian
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Joseph P. Arena
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Jixin Wang
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Denise Wunderler
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Ken Liu
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Gregory J. Kaczorowski
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Lex H.T. Van der Ploeg
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Barry Ganetzky
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Charles J. Cohen
From the *Department of Genetics and Molecular Biology, ‡Department of Membrane Biochemistry and Biophysics, and §Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065; and ‖Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
Address correspondence to Dr. Charles Cohen, Merck Research Laboratories, P.O. Box 2000, Rm. 80N-31C, Rahway, NJ 07065. FAX: 908-594-3925; E-mail: [email protected]
1
Abbreviations used in this paper: ATX-II, toxin II from Anemonia sulcata; TTX, tetrodotoxin.
R.A.G. Reenan's current address is Department of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030.
Received:
December 30 1996
Accepted:
May 14 1997
Online ISSN: 1540-7748
Print ISSN: 0022-1295
1997
J Gen Physiol (1997) 110 (2): 119–133.
Article history
Received:
December 30 1996
Accepted:
May 14 1997
Citation
Jeffrey W. Warmke, Robert A.G. Reenan, Peiyi Wang, Su Qian, Joseph P. Arena, Jixin Wang, Denise Wunderler, Ken Liu, Gregory J. Kaczorowski, Lex H.T. Van der Ploeg, Barry Ganetzky, Charles J. Cohen; Functional Expression of Drosophila para Sodium Channels : Modulation by the Membrane Protein TipE and Toxin Pharmacology. J Gen Physiol 1 August 1997; 110 (2): 119–133. doi: https://doi.org/10.1085/jgp.110.2.119
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