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Review
. 2010 Aug 20;107(4):457-65.
doi: 10.1161/CIRCRESAHA.110.224592.

Defining a new paradigm for human arrhythmia syndromes: phenotypic manifestations of gene mutations in ion channel- and transporter-associated proteins

Michael J Ackerman  1 , Peter J Mohler
Affiliations
Review

Defining a new paradigm for human arrhythmia syndromes: phenotypic manifestations of gene mutations in ion channel- and transporter-associated proteins

Michael J Ackerman et al. Circ Res. .

Abstract

Over the past 15 years, gene mutations in cardiac ion channels have been linked to a host of potentially fatal human arrhythmias including long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. More recently, a new paradigm for human arrhythmia has emerged based on gene mutations that affect the activity of cardiac ion channel- and transporter- associated proteins. As part of the Circulation Research thematic series on inherited arrhythmias, this review focuses on the emerging field of human arrhythmias caused by dysfunction in cytosolic gene products (including ankyrins, yotiao, syntrophin, and caveolin-3) that regulate the activities of key membrane ion channels and transporters.

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Figures

Figure 1
Figure 1. Ankyrin-B organizes membrane ion channels and transporters in ventricular cardiomyocytes
Model depicts multifunctional role for ankyrin-B in _targeting and clustering Na/Ca exchanger, Na/K ATPase, and IP3 receptor at transverse-tubule/sarcoplasmic reticulum domains in ventricular cardiomyocytes. Ankyrin-B also organizes structural (obscurin, betaII spectrin) and signaling (protein phosphatase 2A) in myocytes.
Figure 2
Figure 2. Cardiac voltage-gated sodium channel macromolecular complex
Model illustrates cardiac voltage-gated sodium channel alpha (Nav1.5, black) and beta (white) subunits, as well as associated complex members including ankyrin-G, alpha1 syntrophin, nNOS, and PMCA4b. Nav1.5 is also associated with caveolin-3 although the mechanism for the interaction is still unclear.
Figure 3
Figure 3. Cardiac IKs and IKr complexes in heart
In addition to interactions of channel alpha and beta subunits for both complexes, the Kv7.1 alpha subunit encoded by KCNQ1 also associates with yotiao (AKAP9) in heart which recruits signaling molecules protein phosphatase 1 (PP1), protein kinase A (PKA), and phosphodiesterase 4D3 (PDE4D3) to the IKs complex. In brain, yotiao also associates with specific isoforms of adenylyl cyclase (AC).
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References

    1. Domanski MJ, Zipes DP, Schron E. Treatment of sudden cardiac death. Current understandings from randomized trials and future research directions. Circulation. 1997;95:2694–2699. - PubMed
    1. Spooner PM, Albert C, Benjamin EJ, Boineau R, Elston RC, George AL, Jr, Jouven X, Kuller LH, MacCluer JW, Marban E, Muller JE, Schwartz PJ, Siscovick DS, Tracy RP, Zareba W, Zipes DP. Sudden cardiac death, genes, and arrhythmogenesis: consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I. Circulation. 2001;103:2361–2364. - PubMed
    1. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998;98:2334–2351. - PubMed
    1. Cunha SR, Mohler PJ. Ankyrin protein networks in membrane formation and stabilization. J Cell Mol Med. 2009;13:4364–4376. - PMC - PubMed
    1. Mohler PJ, Rivolta I, Napolitano C, Lemaillet G, Lambert S, Priori SG, Bennett V. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A. 2004;101:17533–17538. - PMC - PubMed

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