Requirement of a Macromolecular Signaling Complex for 
Adrenergic Receptor Modulation of the KCNQ1-KCNE1 Potassium Channel
Steven O. Marx,*
Junko Kurokawa,*
Steven Reiken,
Howard Motoike,
Jeanine D'Armiento,
Andrew R. Marks,
Robert S. Kass
Sympathetic nervous system (SNS) regulation of cardiac action
potential duration (APD) is mediated by 
adrenergic receptor (AR)
activation, which increases the slow outward potassium ion current
(IKS). Mutations in two human
IKS channel subunits, hKCNQ1 and hKCNE1, prolong
APD and cause inherited cardiac arrhythmias known as LQTS (long QT
syndrome). We show that AR modulation of IKS
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 IKS.
Department of Pharmacology, Center for Molecular Cardiology,
Department of Medicine, College of Physicians and Surgeons of Columbia
University, New York, NY 10032, USA.
*
These authors contributed equally to this report.
To whom correspondence should be addressed.
E-mail: rsk20{at}columbia.edu
