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Background
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GxTx-1E was isolated from the venom of Chilobrachys jingzhao (Chinese earth tiger tarantula). It was shown to block Kv2.1/KCNB1, Kv2.2/KCNB2 and Kv4.3/KCND3 channels without significant effect on Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.5/KCNA5, Kv3.2/KCNC2, Cav1.2/CACNA1C, Cav2.2/CACNA1B, Nav1.5/SCN5A, Nav1.7/SCN9A or Nav1.8/SCN10A channels. GxTx-1E inhibits Kv2.1 with an IC50 value of 1 nM and Kv2.2 with an IC50 value of 3 nM. Block of Kv4.3 occurs at 10-20 fold higher concentrations. It acts as a gating modifier since it shifts the voltage-dependence of Kv2.1 K+ currents towards depolarized potentials. In pancreatic b cells, it enhances glucose-stimulated insulin secretion by broadening the cell action potential and enhancing calcium oscillations.
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