title: Toad toxin-resistant snake (Thamnophis elegans) expresses high levels of mutant Na+/K+-ATPase mRNA in cardiac muscle.
abstract: Toads are chemically defended by bufadienolides, which are lethal to most predators. These toxins exert their lethal effects by binding to and disabling the Na+/K+-ATPases of cell membranes. Many species of snakes exhibit resistance to the effects of bufadienolides due to target-site insensitivity of the Na+/K+-ATPase. Mutations that confer resistance have previously been identified in ATP1a3, the gene that codes for the Na+/K+-ATPase α-3 paralog. We have found that this mutant gene is expressed at a significantly elevated level in heart tissue compared to gut, kidney, and liver of the bufadienolide-resistant snake, Thamnophis elegans. Furthermore, we found that exposure to bufadienolides elicits a significant increase in the expression levels of ATP1a3 in the heart, but not in the kidneys, liver, or gut 1h after exposure. We suggest that upregulation of ATP1a3 in the heart plays an important role in the physiological processes involved in tolerance of bufadienolides among genetically resistant snakes.
authors.affiliation: Department of Biology, Utah State University, Logan, UT 84322, USA; The Ecology Center, Utah State University, Logan, UT 84322, USA. Electronic address: shab.mohammadi@gmail.com.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Department of Biology, Utah State University, Logan, UT 84322, USA; The Ecology Center, Utah State University, Logan, UT 84322, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Savitzky
authors.affiliation: Molecular Evolutionary Biology, Department of Biology, Universität Hamburg, Hamburg 20146, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lohr
authors.affiliation: Molecular Evolutionary Biology, Department of Biology, Universität Hamburg, Hamburg 20146, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Dobler
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000633:toxicity; D002316:Cardiotonic Agents / Q000633:toxicity; D017812:Colubridae / Q000235:genetics*; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics*; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002018:Bufanolides; D002316:Cardiotonic Agents; D050505:Mutant Proteins; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Bufadienolides; Gene expression; Na(+)/K(+)-ATPase; Snakes; Toxin resistance