Requirement of a macromolecular signaling complex for β adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel

SO Marx, J Kurokawa, S Reiken, H Motoike… - Science, 2002 - science.org
SO Marx, J Kurokawa, S Reiken, H Motoike, J D'Armiento, AR Marks, RS Kass
Science, 2002science.org
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 KSrequires targeting of adenosine 3′, 5′-
monophosphate (cAMP)–dependent protein kinase (PKA) and protein phosphatase 1 (PP1) …
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 humanI 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 KSrequires 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 throughI KS.
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