Gating-related molecular motions in the extracellular domain of the IKs channel: implications for IKs channelopathy.

ABSTRACT: Cardiac slow delayed rectifier (I(Ks)) channel complex consists of KCNQ1 channel and KCNE1 auxiliary subunits. The extracellular juxtamembranous region of KCNE1 is an unstructured loop that contacts multiple KCNQ1 positions in a gating-state-dependent manner. Congenital arrhythmia-related mutations have been identified in the extracellular S1-S2 linker of KCNQ1. These mutations manifest abnormal phenotypes only when coexpressed with KCNE1, pointing to the importance of proper KCNQ1/KCNE1 interactions here in I(Ks) channel function. We investigate the interactions between the KCNE1 loop (positions 36-47) and KCNQ1 S1-S2 linker (positions 140-148) by means of disulfide trapping and voltage clamp techniques. During transitions among the resting-state conformations, KCNE1 positions 36-43 make

SUBMITTER: Wang YH 

PROVIDER: S-EPMC3893887 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature