Structural determinants of phosphatidylinositol 4,5-bisphosphate (PIP2) regulation of BK channel activity through the RCK1 Ca2+ coordination site.

ABSTRACT: Big or high conductance potassium (BK) channels are activated by voltage and intracellular calcium (Ca(2+)). Phosphatidylinositol 4,5-bisphosphate (PIP2), a ubiquitous modulator of ion channel activity, has been reported to enhance Ca(2+)-driven gating of BK channels, but a molecular understanding of this interplay or even of the PIP2 regulation of this channel's activity remains elusive. Here, we identify structural determinants in the KDRDD loop (which follows the αA helix in the RCK1 domain) to be responsible for the coupling between Ca(2+) and PIP2 in regulating BK channel activity. In the absence of Ca(2+), RCK1 structural elements limit channel activation through a decrease in the channel's PIP2 apparent affinity. This inhibitory influence of BK channel activation can be relieved by

SUBMITTER: Tang QY 

PROVIDER: S-EPMC4081927 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature