KCNE3 acts by promoting voltage sensor activation in KCNQ1

Abstract

Significance The association of KCNE3 beta subunits to KCNQ1 channels turns voltage-dependent KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels that are important for the transport of water and salts across epithelial cell layers. Because KCNQ1/KCNE3 channels are necessary for water and salt secretion in the colon, KCNQ1/KCNE3 channels are a potential drug target in the treatment of secretory diarrhea. Mutations in KCNE3 have also been associated with diseases such as cardiac arrhythmia and tinnitus. We here propose a model for how KCNE3 turns KCNQ1 into a voltage-independent channel. Our model will allow for a better understanding of how mutations in KCNQ1 and KCNE3 cause diseases and how to design drugs to treat these diseases.