Morin, Trevor J.Kobertz, William R.2022-08-232022-08-232007-06-292008-09-22<p>ACS Chem Biol. 2007 Jul 20;2(7):469-73. Epub 2007 Jun 29. <a href="http://dx.doi.org/10.1021/cb700089s">Link to article on publisher's site</a></p>1554-8937 (Electronic)10.1021/cb700089s17602620https://hdl.handle.net/20.500.14038/33781KCNE transmembrane peptides are a family of modulatory beta-subunits that assemble with voltage-gated K+ channels, producing the diversity of potassium currents needed for proper function in a variety of tissues. Although all five KCNE transcripts have been found in cardiac and other tissues, it is unclear whether two different KCNE peptides can assemble with the same K+ channel to form a functional complex. Here, we describe the derivatization of a scorpion toxin that irreversibly inhibits KCNQ1 (Q1) K+ channel complexes that contain a specific KCNE peptide. Using this KCNE sensor, we show that heteromeric complexes form, and the functional output from these complexes reveals a hierarchy in KCNE modulation of Q1 channels: KCNE3 > KCNE1 >> KCNE4. Furthermore, our results demonstrate that Q1/KCNE1/KCNE4 complexes also generate a slowly activating current that has been previously attributed to homomeric Q1/KCNE1 complexes, providing a potential functional role for KCNE4 peptides in the heart.en-USJournal Articlehttps://escholarship.umassmed.edu/gsbs_sp/441635316gsbs_sp/441