GSBS Student Publications

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

DOI of Published Version

10.1021/cb700089s

Related Resources

Link to Article in PubMed

Journal Title

ACS chemical biology

PubMed ID

17602620

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