KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions

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Barro-Soria, ReneUniversity of Miami, FL 33136 USA (author)

KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions

Article/chapterEnglish2017

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2017-08-14
NATL ACAD SCIENCES,2017
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LIBRIS-ID:oai:DiVA.org:liu-140962
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-140962URI
https://doi.org/10.1073/pnas.1710335114DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Funding Agencies|NIH [R01-GM109762, R01-HL131461]; American Heart Association Postdoctoral Fellowship [13POST17000057]; Taking Flight Award from Citizens United for Research in Epilepsy [414889]; NIH K01 Award from the National Institute of Neurological Disorders and Stroke [1K01NS096778-01A1]; Swedish Research Council [2011-6806]
KCNE beta-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the heart, KCNE1 associates with the alpha-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coassembles with KCNQ1 to form K+ channels that are voltage-independent K+ channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphosphate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-to-gate coupling.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
KCNQ1; KCNE1; KCNE3; Kv7.1; voltage clamp fluorometry

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Ramentol, RosamaryUniversity of Miami, FL 33136 USA (author)
Liin, SaraLinköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten,University of Miami, FL 33136 USA(Swepub:liu)sarbo42 (author)
Perez, Marta E.University of Miami, FL 33136 USA (author)
Kass, Robert S.Columbia University, NY 10032 USA (author)
Larsson, H. PeterUniversity of Miami, FL 33136 USA (author)
University of Miami, FL 33136 USAAvdelning för neurobiologi (creator_code:org_t)

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In:Proceedings of the National Academy of Sciences of the United States of America: NATL ACAD SCIENCES114:35, s. E7367-E73760027-84241091-6490

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