Glycine311, a determinant of paxilline block in BK channels: a novel bend in the BK S6 helix.

ABSTRACT: The tremorogenic fungal metabolite, paxilline, is widely used as a potent and relatively specific blocker of Ca(2+)- and voltage-activated Slo1 (or BK) K(+) channels. The pH-regulated Slo3 K(+) channel, a Slo1 homologue, is resistant to blockade by paxilline. Taking advantage of the marked differences in paxilline sensitivity and the homology between subunits, we have examined the paxilline sensitivity of a set of chimeric Slo1/Slo3 subunits. Paxilline sensitivity is associated with elements of the S5-P loop-S6 module of the Slo1 channel. Replacement of the Slo1 S5 segment or the second half of the P loop results in modest changes in paxilline sensitivity. Replacing the Slo1 S6 segment with the Slo3 sequence abolishes paxilline sensitivity. An increase in paxilline affinity and changes in

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC2860595 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature