Title

A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology; Massachusetts Biologic Laboratories

Publication Date

2007-06-29

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Animal Experimentation and Research | Genetic Phenomena | Inorganic Chemicals | Investigative Techniques | Tissues

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.

DOI of Published Version

10.1021/cb700089s

Source

ACS Chem Biol. 2007 Jul 20;2(7):469-73. Epub 2007 Jun 29. Link to article on publisher's site

Journal/Book/Conference Title

ACS chemical biology

Related Resources

Link to Article in PubMed

PubMed ID

17602620

Link to Full Text

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