Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Ito1 in cardiac electrogenesis
作者： Sylvie Diochot , Milou-Daniel Drici , Danielle Moinier , Michel Fink , Michel Lazdunski
关键词: Gating 、 Patch clamp 、 Potassium channel 、 Chemistry 、 KvLQT1 、 Voltage-gated potassium channel 、 Shal Potassium Channels 、 QT interval 、 Internal medicine 、 Endocrinology 、 hERG
摘要: 1. In the present study, two new peptides, phrixotoxins PaTx1 and PaTx2 (29-31 amino acids), which potently block A-type potassium currents, have been purified from venom of tarantula Phrixotrichus auratus. 2. Phrixotoxins specifically Kv4.3 Kv4.2 currents that underlie I(to1), with an 5 < IC50 70 nM, by altering gating properties these channels. 3. Neither are Shaker (Kv1), Shab (Kv2) Shaw (Kv3) subfamilies nor HERG, KvLQT1/IsK, inhibited appear specific Shal (Kv4) subfamily also I(to1) in isolated murine cardiomyocytes. 4. order to evaluate physiological consequences Ito1 inhibition, mice were injected intravenously PaTx1, resulted numerous transient cardiac adverse reactions including occurrence premature ventricular beats, tachycardia different degrees atrioventricular block. 5. The analysis mouse electrocardiogram showed a dose-dependent prolongation QT interval, chosen as surrogate marker for their repolarization, 249 +/- 11 265 8 ms (P 0.05). 6. It was concluded phrixotoxins, blockers hence will enable further studies channel and/or expression.
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