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Adrenergic Regulation and Heritable Arrhythmias: Key Roles of the Slowly Activating Heart I Ks Potassium Channel

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Abstract

The slowly activating delayed rectifier I Ks channel plays a crucial role in heart repolarization and is regulated by β-adrenergic receptor (β-AR) stimulation. I Ks channels are comprised of a pore forming subunit, KCNQ1, as well as an auxiliary subunit, KCNE1, and are regulated by the sympathetic nervous system through KCNQ1 association with AKAP9 (Yotiao): AKAP9 recruits PKA, a phosphatase, adenylate cyclase, and a phosphodiesterase to the channel which enables fine regulation of the phosphorylated state of a key serine residue located in the KCNQ1 N-terminus. This chapter reviews work has elucidated the molecular mechanisms underlying sympathetic regulation of I Ks and the role of mutations of these genes in heritable arrhythmias, and summarizes the direction of current and future research.

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Authors and Affiliations

  1. Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W. 168th St., New York, NY, 10032, USA

    David Y. Chung, Kevin J. Sampson & Robert S. Kass

Authors
  1. David Y. Chung
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  2. Kevin J. Sampson
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  3. Robert S. Kass
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Corresponding author

Correspondence to Robert S. Kass .

Editor information

Editors and Affiliations

  1. Life Sciences Academy, Usman Enclave 103, Lucknow, 226024, India

    Onkar N. Tripathi

  2. Medizinische Fakultät, Inst. für Pharmakologie u. Toxikologie, TU Dresden, Fetscherstraße 74, Dresden, 01307, Germany

    Ursula Ravens

  3. Cardiovascular Research &, Training Inst. (CVRTI), University of Utah, South 2000 East 95, Salt Lake City, 84112-5000, Utah, USA

    Michael C. Sanguinetti

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Chung, D.Y., Sampson, K.J., Kass, R.S. (2011). Adrenergic Regulation and Heritable Arrhythmias: Key Roles of the Slowly Activating Heart I Ks Potassium Channel. In: Tripathi, O., Ravens, U., Sanguinetti, M. (eds) Heart Rate and Rhythm. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17575-6_24

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