A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology; Massachusetts Biologic Laboratories
Medical Subject Headings
Amino Acid Sequence; Animals; KCNQ1 Potassium Channel; Mutagenesis, Site-Directed; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Scorpion Venoms; Xenopus
Life Sciences | Medicine and Health Sciences
KCNE 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.
Rights and Permissions
Citation: ACS Chem Biol. 2007 Jul 20;2(7):469-73. Epub 2007 Jun 29. Link to article on publisher's site
DOI of Published Version
ACS chemical biology
Morin, Trevor J. and Kobertz, William R., "A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes" (2007). GSBS Student Publications. 441.