The S631A mutation causes a mechanistic switch in the block of hERG channels by CnErg1.
We have studied the interaction of CnErg1, a member of the gamma-KTX subfamily of scorpion toxins with the inactivation-deficient S631A hERG channel. In the background of this mutation, we observed a mechanistic switch from turret block, characteristic of the action of gamma-KTXs on Kv11-type channels, to pore plugging, characteristic of alpha-KTX block of Kv1-type channels. We suggest this reflects destabilization of the outer pore (turret region) of hERG allowing access of the toxin molecule to directly plug the conduction pathway.
Hill
Adam P
AP
Victor Chang Cardiac Research Institute, New South Wales, Australia.
Campbell
T J
TJ
Bansal
P S
PS
Kuchel
P W
PW
Vandenberg
J I
JI
D019943:Amino Acid Substitution; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D012604:Scorpion Venoms / Q000633:toxicity*
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D012604:Scorpion Venoms; C118951:ergotoxin, Centruroides noxius