Conserved single residue in the BK @entity972 channel required for activation by @entity167 and intoxication in XXXX .

@entity1 @entity70798 @entity1522 @entity2199 @entity70800 @entity167 @entity4030 @entity972 @entity70799 @entity1068
@entity167 directly modulates the BK @entity972 channel to alter behaviors in species ranging from invertebrates to @entity1 . In the @entity2199 @entity2199 , mutations that eliminate the BK channel, @entity70798 , convey dramatic resistance to intoxication by @entity1068 . We hypothesized that certain conserved @entity1522 are critical for @entity1068 modulation, but not for basal channel function. To identify such residues, we screened @entity2199 strains with different missense mutations in the @entity70798 channel. A strain with the @entity70798 missense mutation @entity70799 in the RCK1 domain was highly resistant to intoxication. This mutation did not interfere with other BK channel-dependent behaviors, suggesting that the mutant channel retained normal in vivo function. Knock-in of wild-type versions of the worm or @entity1 BK channel rescued intoxication and other BK channel-dependent behaviors in a @entity4030 -null mutant background. In contrast, knock-in of the worm @entity70799 or equivalent @entity1 @entity70800 mutant BK channel selectively rescued BK channel-dependent behaviors while conveying resistance to intoxication. Single-channel patch-clamp recordings confirmed that the @entity1 BK channel engineered with the @entity70800 missense mutation was insensitive to activation by @entity1068 , but otherwise had normal conductance, @entity972 selectivity, and only subtle differences in voltage dependence. Together, our behavioral and electrophysiological results demonstrate that the @entity70800 mutation selectively disrupts @entity1068 modulation of the BK channel. The @entity70800 mutation may alter a binding site for @entity1068 and/or interfere with @entity1068 -induced conformational changes that are critical for behavioral responses to @entity1068 .
