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• W2040483643 endingPage "344" @default.
• W2040483643 startingPage "334" @default.
• W2040483643 abstract "Certain amphibians provide themselves with a chemical defense by accumulating lipophilic alkaloids into skin glands from dietary arthropods. Examples of such alkaloids are pumiliotoxins (PTXs). In general, PTXs are known as positive modulators of voltage-gated sodium channels (VGSCs). Unlike other PTXs, PTX 251D does not share this characteristic. However, mice and insect studies showed that PTX 251D is highly toxic and to date the basis of its toxicity remains unknown. In this work, we searched for the possible target of PTX 251D. The toxin was therefore made synthetically and tested on four VGSCs (mammalian rNav1.2/β1, rNav1.4/β1, hNav1.5/β1 and insect Para/tipE) and five voltage-gated potassium channels (VGPCs) (mammalian rKv1.1-1.2, hKv1.3, hKv11.1 (hERG) and insect Shaker IR) expressed heterologously in Xenopus laevis oocytes, using the two-electrode voltage clamp technique. PTX 251D not only inhibited the Na+ influx through the mammalian VGSCs but also affected the steady-state activation and inactivation. Interestingly, in the insect ortholog, the inactivation process was dramatically affected. Additionally, PTX 251D inhibited the K+ efflux through all five tested VGPCs and slowed down the deactivation kinetics of the mammalian VGPCs. hKv1.3 was the most sensitive channel, with an IC50 value 10.8±0.5 μM. To the best of our knowledge this is the first report of a PTX affecting VGPCs." @default.
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• W2040483643 date "2008-03-01" @default.
• W2040483643 modified "2023-10-16" @default.
• W2040483643 title "Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: A “joint venture” alkaloid from arthropods and amphibians" @default.
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• W2040483643 doi "https://doi.org/10.1016/j.toxicon.2007.10.011" @default.
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