Evolution of resistance to scorpion neurotoxins

描述（由申请人提供）：亚利桑那树皮蝎（Centruroides exilicauda）和条纹树皮蝎（C. vittatus）产生神经毒素，选择性地结合神经和肌肉兴奋膜中的电压门控制离子通道，产生神经和神经肌肉系统的高度兴奋性。南方蚱蜢鼠（Onychomys torridus）和米恩斯蚱蜢鼠（O. arenicola）是美国沙漠中贪婪的蝎子捕食者。南方和米恩斯的蚱蜢老鼠对树皮蝎毒液表现出生理抵抗力。蚱蜢种群的毒液抗性变异与树皮蝎同属和异属的地理格局共变。电生理实验表明，蚱蜢神经和肌肉中的离子通道对蝎子神经毒素不敏感。该项目的目的是确定抗性小鼠离子通道不敏感的分子遗传基础，表征其种群间抗性水平表型差异的分子变异，并评估与毒素抗性有关的基因选择模式。将检查离子通道编码基因的结构和功能变化，使毒素不敏感。

DESCRIPTION (provided by applicant): The Arizona bark scorpion (Centruroides exilicauda) and the striped bark scorpion (C. vittatus) produce neurotoxins that selectively bind voltage-gated ion channels in excitable membranes of nerve and muscle, producing hyper-excitability of the nervous and neuromuscular systems. Southern grasshopper mice (Onychomys torridus) and Mearns' grasshopper mice (O. arenicola) are voracious predators of scorpions in U.S. deserts. Southern and Mearns' grasshopper mice demonstrate physiological resistance to bark scorpion venom. Variability in venom resistance among grasshopper mice populations co-varies with geographic patterns of bark scorpion sympatry and allopatry. Electrophysiological assays show that ion channels in the nerve and muscle of grasshopper mice are insensitive to scorpion neurotoxins. The purpose of the proposed project is to determine the molecular genetic basis of ion channel insensitivity in resistant mice, to characterize the molecular variation underlying phenotypic differences in resistance levels among their populations, and to assess patterns of selection on genes involved in toxin resistance. Ion channel encoding genes will be examined for structural and functional changes that impart insensitivity to toxins.