Ion Channel Trafficking: Control of Ion Channel Density As a Target for Arrhythmias?

Overview

Journal Front Physiol

Date 2017 Nov 2

PMID 29089904

Citations 13

Authors

Elise Balse

Hannah E Boycott

Affiliations

Soon will be listed here.

Abstract

The shape of the cardiac action potential (AP) is determined by the contributions of numerous ion channels. Any dysfunction in the proper function or expression of these ion channels can result in a change in effective refractory period (ERP) and lead to arrhythmia. The processes underlying the correct targeting of ion channels to the plasma membrane are complex, and have not been fully characterized in cardiac myocytes. Emerging evidence highlights ion channel trafficking as a potential causative factor in certain acquired and inherited arrhythmias, and therapies which target trafficking as opposed to pore block are starting to receive attention. In this review we present the current evidence for the mechanisms which underlie precise control of cardiac ion channel trafficking and targeting.

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References

Sanguinetti M, Curran M, Zou A, Shen J, Spector P, Atkinson D . Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature. 1996; 384(6604):80-3. DOI: 10.1038/384080a0. View

Rajamani S, Anderson C, Anson B, January C . Pharmacological rescue of human K(+) channel long-QT2 mutations: human ether-a-go-go-related gene rescue without block. Circulation. 2002; 105(24):2830-5. DOI: 10.1161/01.cir.0000019513.50928.74. View

Sanguinetti M, Tristani-Firouzi M . hERG potassium channels and cardiac arrhythmia. Nature. 2006; 440(7083):463-9. DOI: 10.1038/nature04710. View

Lundbaek J, Birn P, Girshman J, Hansen A, Andersen O . Membrane stiffness and channel function. Biochemistry. 1996; 35(12):3825-30. DOI: 10.1021/bi952250b. View

Valdivia C, Tester D, Rok B, Porter C, Munger T, Jahangir A . A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res. 2004; 62(1):53-62. DOI: 10.1016/j.cardiores.2004.01.022. View

Van Wagoner D, Pond A, McCarthy P, Trimmer J, Nerbonne J . Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res. 1997; 80(6):772-81. DOI: 10.1161/01.res.80.6.772. View

Mehta A, Sequiera G, Ramachandra C, Sudibyo Y, Chung Y, Sheng J . Re-trafficking of hERG reverses long QT syndrome 2 phenotype in human iPS-derived cardiomyocytes. Cardiovasc Res. 2014; 102(3):497-506. DOI: 10.1093/cvr/cvu060. View

Boycott H, Barbier C, Eichel C, Costa K, Martins R, Louault F . Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes. Proc Natl Acad Sci U S A. 2013; 110(41):E3955-64. PMC: 3799377. DOI: 10.1073/pnas.1309896110. View

Furutani M, Trudeau M, Hagiwara N, Seki A, Gong Q, Zhou Z . Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel. Circulation. 1999; 99(17):2290-4. DOI: 10.1161/01.cir.99.17.2290. View

10.

Kong C, Bursac N, Tung L . Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes. J Appl Physiol (1985). 2005; 98(6):2328-36. DOI: 10.1152/japplphysiol.01084.2004. View

11.

Hong T, Smyth J, Chu K, Vogan J, Fong T, Jensen B . BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart Rhythm. 2011; 9(5):812-20. PMC: 3306544. DOI: 10.1016/j.hrthm.2011.11.055. View

12.

Ren X, Liu G, Organ-Darling L, Zheng R, Roder K, Jindal H . Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines. Am J Physiol Heart Circ Physiol. 2010; 299(5):H1525-34. PMC: 2993209. DOI: 10.1152/ajpheart.00479.2009. View

13.

Trudeau M, Warmke J, Ganetzky B, Robertson G . HERG, a human inward rectifier in the voltage-gated potassium channel family. Science. 1995; 269(5220):92-5. DOI: 10.1126/science.7604285. View

14.

Biliczki P, Girmatsion Z, Brandes R, Harenkamp S, Pitard B, Charpentier F . Trafficking-deficient long QT syndrome mutation KCNQ1-T587M confers severe clinical phenotype by impairment of KCNH2 membrane localization: evidence for clinically significant IKr-IKs alpha-subunit interaction. Heart Rhythm. 2009; 6(12):1792-801. DOI: 10.1016/j.hrthm.2009.08.009. View

15.

Morad M, Javaheri A, Risius T, Belmonte S . Multimodality of Ca2+ signaling in rat atrial myocytes. Ann N Y Acad Sci. 2005; 1047:112-21. DOI: 10.1196/annals.1341.010. View

16.

Kaufman E, Ficker E . Is restoration of intracellular trafficking clinically feasible in the long QT syndrome?: The example of HERG mutations. J Cardiovasc Electrophysiol. 2003; 14(3):320-2. DOI: 10.1046/j.1540-8167.2003.02363.x. View

17.

Kupershmidt S, Yang T, Chanthaphaychith S, Wang Z, Towbin J, Roden D . Defective human Ether-à-go-go-related gene trafficking linked to an endoplasmic reticulum retention signal in the C terminus. J Biol Chem. 2002; 277(30):27442-8. DOI: 10.1074/jbc.M112375200. View

18.

Ehrlich J, Pourrier M, Weerapura M, Ethier N, Marmabachi A, Hebert T . KvLQT1 modulates the distribution and biophysical properties of HERG. A novel alpha-subunit interaction between delayed rectifier currents. J Biol Chem. 2003; 279(2):1233-41. DOI: 10.1074/jbc.M309087200. View

19.

Shy D, Gillet L, Abriel H . Targeting the sodium channel NaV1.5 to specific membrane compartments of cardiac cells: not a simple task!. Circ Res. 2014; 115(11):901-3. DOI: 10.1161/CIRCRESAHA.114.305305. View

20.

SPACH M . Anisotropy of cardiac tissue: a major determinant of conduction?. J Cardiovasc Electrophysiol. 1999; 10(6):887-90. DOI: 10.1111/j.1540-8167.1999.tb00271.x. View