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The Journal of Neuroscience, June 1, 2002, 22(11):4364-4371

Domain 2 of Drosophila Para Voltage-Gated Sodium Channel Confers Insect Properties to a Rat Brain Channel

Iris Shichor^{1, 3}, Eliahu Zlotkin³, Nitza Ilan^{1, 2}, Dodo Chikashvili¹, Walter Stuhmer⁴, Dalia Gordon², and Ilana Lotan¹

Departments of ¹ Physiology and Pharmacology, Sackler School of Medicine and ² Plant Sciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat-Aviv, Israel, ³ Department of Cell and Animal Biology, Institute of Life Sciences, The Hebrew University, 91904 Jerusalem, Israel, and ⁴ Max-Planck-Institut fur Experimentelle Medizin, D-37075 Gottingen, Germany

The ability of the excitatory anti-insect-selective scorpion toxin AahIT (Androctonus australis hector) to exclusively bind to and modify the insect voltage-gated sodium channel (NaCh) makes it a unique tool to unravel the structural differences between mammalian and insect channels, a prerequisite in the design of selective pesticides. To localize the insect NaCh domain that binds AahIT, we constructed a chimeric channel composed of rat brain NaCh -subunit (rBIIA) in which domain-2 (D2) was replaced by that of Drosophila Para (paralytic temperature-sensitive). The choice of D2 was dictated by the similarity between AahIT and scorpion -toxins pertaining to both their binding and action and the essential role of D2 in the -toxins binding site on mammalian channels. Expression of the chimera rBIIA-ParaD2 in Xenopus oocytes gave rise to voltage-gated and TTX-sensitive NaChs that, like rBIIA, were sensitive to scorpion -toxins and regulated by the auxiliary subunit ₁ but not by the insect TipE. Notably, like Drosophila Para/TipE, but unlike rBIIA/₁, the chimera gained sensitivity to AahIT, indicating that the phyletic selectivity of AahIT is conferred by the insect NaCh D2. Furthermore, the chimera acquired additional insect channel properties; its activation was shifted to more positive potentials, and the effect of -toxins was potentiated. Our results highlight the key role of D2 in the selective recognition of anti-insect excitatory toxins and in the modulation of NaCh gating. We also provide a methodological approach to the study of ion channels that are difficult to express in model expression systems.

Key words: Na channel; insect selectivity; Xenopus oocytes; scorpion toxin; gating; Drosophila Para

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22114364-08$05.00/0

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