کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2065912 1076949 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: A “joint venture” alkaloid from arthropods and amphibians
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: A “joint venture” alkaloid from arthropods and amphibians
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicon - Volume 51, Issue 3, 1 March 2008, Pages 334–344
نویسندگان
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