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Requirement of a Macromolecular Signaling Complex for β Adrenergic Receptor Modulation of the KCNQ1-KCNE1 Potassium Channel
Abstract
Sympathetic nervous system (SNS) regulation of cardiac action potential duration (APD) is mediated by β adrenergic receptor (βAR) activation, which increases the slow outward potassium ion current ( I KS ). Mutations in two human I KS channel subunits, hKCNQ1 and hKCNE1, prolong APD and cause inherited cardiac arrhythmias known as LQTS (long QT syndrome). We show that βAR modulation of I KS requires targeting of adenosine 3′,5′-monophosphate (cAMP)–dependent protein kinase (PKA) and protein phosphatase 1 (PP1) to hKCNQ1 through the targeting protein yotiao. Yotiao binds to hKCNQ1 by a leucine zipper motif, which is disrupted by an LQTS mutation (hKCNQ1-G589D). Identification of the hKCNQ1 macromolecular complex provides a mechanism for SNS modulation of cardiac APD through I KS .
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Hamill, O. P., Marty, A., Neher, E., Sakmann, B., & Sigworth, F. J. (1981) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00656997 · Cited by 18,436
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Metadata
- Authors
- Marx, S. O., Kurokawa, J., Reiken, S., Motoike, H., D'Armiento, J., Marks, A. R., & Kass, R. S.
- Venue
- Science
- Published
- 2002-01-18
- Volume
- 295
- Issue
- 5554
- Pages
- 496-499
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2024732013
- Cited by
- 710
- References
- 1
- FWCI
- 29.89
- Type
- journal article
- Language
- en
- Open access
- closed
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- Marx, S. O., Kurokawa, J., Reiken, S., Motoike, H., D'Armiento, J., Marks, A. R., & Kass, R. S. (2002). Requirement of a Macromolecular Signaling Complex for β Adrenergic Receptor Modulation of the KCNQ1-KCNE1 Potassium Channel. Science. https://doi.org/10.1126/science.1066843
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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