Charybdotoxin, potassium channel

Gao, Y. D., and Garcia, M. L. 2003. Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels selectivity between voltage-gated and Maxi-K channels. Proteins 52 146-154. 

Voltage-gated potassium channels also have a number of different binding sites. Similar to sodium channels, there is a binding site for peptide toxins at the outer vestibule of the pore. This binding site has been identified by site-directed mutagenesis for different peptide toxins, e.g., for the toxin ShK from a sea anemone, which blocks Kvl.3, or for Charybdotoxin, which blocks various potassium channels [19, 20],... 

Note. Barium block of K channels is very voltage dependent. Block by charybdotoxin and iberiotoxin is also voltage dependent. TEA+ block is voltage-dependent but not very steep. In all aforementioned cases the block increases with membrane hyperpolarization. The bold values indicate the relative selective concentration for the inhibitor of that type of potassium channel. K, = half-inhibition constant. For references, see text. 

Certain synthetic potassium channel openers have been shown to activate K a channels, such as NS-004 (Sargenteta/., 1993)andNS-1619. However, iberiotoxin was unable to reverse the functional effects of NS-004, and therefore its mechanism of action may also involve inhibition of calcium current rather than activation of K a channels. Some drugs (e.g., cro-makalim) that activate K -p channels have also been shown to activate K channels in aortic smooth muscle cells but not in other types of arterial smooth muscle. Since blockers of K a channels (charybdotoxin and <1 mM TEA+) had no effect on membrane potential hyperpolarizations or dilations to any of... 

In 2003, Offertaler et al. provided further evidence for the endothelial anandamide receptor. Specifically, they reported that a novel cannabidiol analog, 0-1918, opposed the relaxant effects of anandamide and abn-cbd, the in vivo hypotensive effects of abn-cbd, and the phosphorylation of p42/44 MAP kinase induced by abn-cbd in endothelial cells. These actions of 0-1918 were independent of classical cannabinoid and vanilloid receptors, and this led the authors to conclude that 0-1918 was a selective antagonist of the endothelial anandamide receptor. It was suggested that the endothehum-dependent relaxation to abn-cbd and anandamide is G protein coupled to MAP kinase activation and charybdotoxin-sensifive potassium channels but not to nitric oxide. Taken together, the authors proposed that the novel receptor may be coupled to the release of the EDHF. 

Yu L, Sun C, Song D, Shen J, Xu N, Gunasekera A, HajdukPJ, Olejniczak ET (2005) Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex. Biochemistry 44 15834-15841... 

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