A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes.
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.
Morin
Trevor J
TJ
Kobertz
William R
WR
D000595:Amino Acid Sequence; D000818:Animals; D051657:KCNQ1 Potassium Channel / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology*; D014981:Xenopus
C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms