Title
A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology; Massachusetts Biologic Laboratories
Date
7-3-2007
Document Type
Article
Medical Subject Headings
Amino Acid Sequence; Animals; KCNQ1 Potassium Channel; Mutagenesis, Site-Directed; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Scorpion Venoms; Xenopus
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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