Mapping the receptor site for ergtoxin, a specific blocker of ERG channels

Abstract
We show here that ergtoxin (ErgTx) is a bona fide, specific blocker of the human ether‐a‐go‐go‐related gene (HERG) channels. It does not affect the function of either M‐eag or M‐elk channels. A chimeric construction containing a segment of the P‐region of M‐eag channel inserted into the HERG channel drastically diminished or completely abolished the inhibitory effect of ErgTx, whereas chimeras of the P‐region of HERG channel into M‐eag channels recovered the inhibitory effect. From the P‐region point mutants of HERG channel assays, only the mutant N598Q shows about 25% decrement of the ErgTx inhibitory effect. ErgTx recognizes the P‐region of HERG channels, blocking the channel function with a K d in the order of 12 nM.