Emerging concepts in the pharmacogenomics of arrhythmias: ion channel trafficking

References

• Grant AO. Cardiac ion channels. Circ. Arrhythm. Electrophysiol.2(2), 185–194 (2009).
   PubMed Web of Science ®Google Scholar
• Nerbonne JM. Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. J. Physiol.525(2), 285–298 (2000).
   PubMed Web of Science ®Google Scholar
• Mays DJ, Foose JM, Philipson LH, Tamkun MM. Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue. J. Clin. Invest.96(1), 282–292 (1995).
   PubMed Web of Science ®Google Scholar
• Amos GJ, Wettwer E, Metzger F, Li Q, Himmel HM, Ravens U. Differences between outward currents of human atrial and subepicardial ventricular myocytes. J. Physiol.491(Pt 1), 31–50 (1996).
   PubMed Web of Science ®Google Scholar
• Wang Z, Fermini B, Nattel S. Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ. Res.73(6), 1061–1076 (1993).
   PubMed Web of Science ®Google Scholar
• Charpentier F, Demolombe S, Escande D. Cardiac channelopathies: from men to mice. Ann. Med.36(s1), 28–34 (2004).
   PubMed Web of Science ®Google Scholar
• Ackerman MJ. The long QT syndrome: ion channel diseases of the heart. Mayo Clin. Proc.73(3), 250–269 (1998).
   PubMed Web of Science ®Google Scholar
• Otway R, Vandenberg JI, Fatkin D. Atrial fibrillation – a new cardiac channelopathy. Heart Lung Circ.16(5), 356–360 (2007).
   PubMedGoogle Scholar
• Chen Y-H, Xu S-J, Bendahhou S et al.KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science299(5604), 251–254 (2003).
   PubMed Web of Science ®Google Scholar
• McPate MJ, Duncan RS, Milnes JT, Witchel HJ, Hancox JC. The N588K- hERG K+ channel mutation in the ‘short QT syndrome’: mechanism of gain-in-function determined at 37 °C. Biochem. Biophys. Res. Commun.334(2), 441–449 (2005).
   PubMed Web of Science ®Google Scholar
• Xia M, Jin Q, Bendahhou S et al. A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem. Biophys. Res. Commun.332(4), 1012–1019 (2005).
   PubMed Web of Science ®Google Scholar
• Yang Y, Xia M, Jin Q et al. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am. J. Hum. Genet.75(5), 899–905 (2004).
   PubMed Web of Science ®Google Scholar
• Page RL, Roden DM. Drug therapy for atrial fibrillation: where do we go from here? Nat. Rev. Drug Discov.4(11), 899–910 (2005).
   PubMed Web of Science ®Google Scholar
• Ruan Y, Liu N, Napolitano C, Priori SG. Therapeutic strategies for long-QT syndrome: does the molecular substrate matter? Circ. Arrhythm. Electrophysiol.1(4), 290–297 (2008).
   PubMed Web of Science ®Google Scholar
• Roden DM. Cellular basis of drug-induced torsades de pointes. Br. J. Pharmacol.154(7), 1502–1507 (2008).
   PubMed Web of Science ®Google Scholar
• Ford JWP, Milnes JTP. New drugs targeting the cardiac ultra-rapid delayed-rectifier current (IKur): rationale, pharmacology and evidence for potential therapeutic value. J. Cardiovasc. Pharmacol.52(2), 105–120 (2008).
   PubMed Web of Science ®Google Scholar
• Johnson AE, van Waes MA. The translocon: a dynamic gateway at the ER membrane. Annu. Rev. Cell Dev. Biol.15(1), 799–842 (1999).
   PubMed Web of Science ®Google Scholar
• Sato Y, Sakaguchi M, Goshima S, Nakamura T, Uozumi N. Integration of Shaker-type K+ channel, KAT1, into the endoplasmic reticulum membrane: Synergistic insertion of voltage-sensing segments, S3–S4, and independent insertion of pore-forming segments, S5–S6. Proc. Natl Acad. Sci. USA99(1), 60–65 (2002).
   PubMed Web of Science ®Google Scholar
• Kosolapov A, Deutsch C. Folding of the voltage-gated K+ channel T1 recognition domain. J. Biol. Chem.278(6), 4305–4313 (2003).
   PubMed Web of Science ®Google Scholar
• Lu J, Robinson JM, Edwards D, Deutsch C. T1–T1 interactions occur in ER membranes while nascent Kv peptides are still attached to ribosomes. Biochemistry40(37), 10934–10946 (2001).
   PubMed Web of Science ®Google Scholar
• Nagaya N, Papazian DM. Potassium channel α and β subunits assemble in the endoplasmic reticulum. J. Biol. Chem.272(5), 3022–3027 (1997).
   PubMed Web of Science ®Google Scholar
• Scott DB, Blanpied TA, Swanson GT, Zhang C, Ehlers MD. An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing. J. Neurosci.21(9), 3063–3072 (2001).
   PubMed Web of Science ®Google Scholar
• Li D, Takimoto K, Levitan ES. Surface expression of Kv1 channels is governed by a C-terminal motif. J. Biol. Chem.275(16), 11597–11602 (2000).
   PubMed Web of Science ®Google Scholar
• Chen J, Sroubek J, Krishnan Y, Li Y, Bian J, McDonald TV. PKA phosphorylation of hERG protein regulates the rate of channel synthesis. Am. J. Physiol. Heart Circ. Physiol.296(5), H1244–1254 (2009).
   Google Scholar
• Xia H, Hornby ZD, Malenka RC. An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits. Neuropharmacology41(6), 714–723 (2001).
   PubMed Web of Science ®Google Scholar
• Zadeh AD, Cheng Y, Xu H et al. Kif5b is an essential forward trafficking motor for the Kv1.5 cardiac potassium channel. J. Physiol.587(19), 4565–4574 (2009).
   PubMed Web of Science ®Google Scholar
• Boehmer C, Laufer J, Jeyaraj S et al. Modulation of the voltage-gated potassium channel Kv1.5 by the SGK1 protein kinase involves inhibition of channel ubiquitination. Cell. Physiol. Biochem.22(5–6), 591–600 (2008).
   PubMedGoogle Scholar
• McEwen DP, Schumacher SM, Li Q et al. Rab-GTPase-dependent endocytic recycling of Kv1.5 in atrial myocytes. J. Biol. Chem.282(40), 29612–29620 (2007).
   PubMed Web of Science ®Google Scholar
• Deutsch C. Potassium channel ontogeny. Annu. Rev. Physiol.64(1), 19–46 (2002).
   PubMed Web of Science ®Google Scholar
• Steele DF, Eldstrom J, Fedida D. Mechanisms of cardiac potassium channel trafficking. J. Physiol.582(1), 17–26 (2007).
   PubMed Web of Science ®Google Scholar
• Walker VE, Wong MJH, Atanasiu R, Hantouche C, Young JC, Shrier A. Hsp40 chaperones promote degradation of the hERG potassium channel. J. Biol. Chem.285(5), 3319–3329 (2009).
   PubMed Web of Science ®Google Scholar
• Abbott GW, Roepke TK. Pharmacogenetics of drug-induced arrhythmias. Expert Rev. Clin. Pharmacol.1(1), 93–104 (2008).
   PubMed Web of Science ®Google Scholar
• Anderson CL, Delisle BP, Anson BD et al. Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation113(3), 365–373 (2006).
   PubMed Web of Science ®Google Scholar
• Rajamani S, Anderson CL, Anson BD, January CT. Pharmacological rescue of human K+ channel long-QT2 mutations: human ether-a-go-go-related gene rescue without block. Circulation105(24), 2830–2835 (2002).
   PubMed Web of Science ®Google Scholar
• Ficker E, Dennis AT, Obejero-Paz CA, Castaldo P, Taglialatela M, Brown AM. Retention in the endoplasmic reticulum as a mechanism of dominant-negative current suppression in human long QT syndrome. J. Mol. Cell. Cardiol.32(12), 2327–2337 (2000).
   PubMed Web of Science ®Google Scholar
• Gong Q, Keeney DR, Molinari M, Zhou Z. Degradation of trafficking-defective long QT syndrome type II mutant channels by the ubiquitin-proteasome pathway. J. Biol. Chem.280(19), 19419–19425 (2005).
   PubMed Web of Science ®Google Scholar
• Keller S, Platoshyn O, Yuan J. Long QT syndrome-associated I593R mutation in hERG potassium channel activates ER stress pathways. Cell Biochem. Biophys.43(3), 365–377 (2005).
   PubMed Web of Science ®Google Scholar
• Ficker E, Obejero-Paz CA, Zhao S, Brown AM. The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (hERG) mutations. J. Biol. Chem.277(7), 4989–4998 (2002).
   PubMed Web of Science ®Google Scholar
• Kaufman ES, Ficker E. Is restoration of intracellular trafficking clinically feasible in the long QT syndrome? J. Cardiovasc. Electrophysiol.14(3), 320–322 (2003).
   PubMed Web of Science ®Google Scholar
• Ficker E, Dennis AT, Wang L, Brown AM. Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel hERG. Circ. Res.92(12), e87–e100 (2003).
   PubMed Web of Science ®Google Scholar
• Nanduri J, Bergson P, Wang N, Ficker E, Prabhakar NR. Hypoxia inhibits maturation and trafficking of hERG K+ channel protein: role of Hsp90 and ROS. Biochem. Biophys. Res. Commun.388(2), 212–216 (2009).
   PubMed Web of Science ®Google Scholar
• Walker VE, Atanasiu R, Lam H, Shrier A. Co-chaperone FKBP38 promotes hERG trafficking. J. Biol. Chem.282(32), 23509–23516 (2007).
   PubMed Web of Science ®Google Scholar
• Akhavan A, Atanasiu R, Noguchi T, Han W, Holder N, Shrier A. Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization. J. Cell Sci.118(13), 2803–2812 (2005).
   PubMed Web of Science ®Google Scholar
• Burke JF, Mogg AE. Suppression of a nonsense mutation in mammalian cells in vivo by the aminoglycoside antibiotics G-418 and paromomycin. Nucl. Acids Res.13(17), 6265–6272 (1985).
   PubMed Web of Science ®Google Scholar
• Yao Y, Teng S, Li N, Zhang Y, Boyden PA, Pu J. Aminoglycoside antibiotics restore functional expression of truncated hERG channels produced by nonsense mutations. Heart Rhythm6(4), 553–560 (2009).
   PubMed Web of Science ®Google Scholar
• Wang L, Wible BA, Wan X, Ficker E. Cardiac glycosides as novel inhibitors of human ether-a-go-go-related gene channel trafficking. J. Pharmacol. Exp. Ther.320(2), 525–534 (2007).
   PubMed Web of Science ®Google Scholar
• Wang L, Dennis AT, Trieu P et al. Intracellular potassium stabilizes human ether-à-go-go-related gene channels for export from endoplasmic reticulum. Mol. Pharmacol.75(4), 927–937 (2009).
   PubMed Web of Science ®Google Scholar
• Guo J, Massaeli H, Xu J et al. Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the hERG channel in human cell lines. J. Clin. Invest.119(9), 2745–2757 (2009).
   PubMed Web of Science ®Google Scholar
• Roden DM, Thompson KA, Hoffman BF, Woosley RL. Clinical features and basic mechanisms of quinidine-induced arrhythmias. J. Am. Coll. Cardiol.8(1 Suppl. A), 73A–78A (1986).
   PubMed Web of Science ®Google Scholar
• Berthet M, Denjoy I, Donger C et al. C-terminal hERG mutations: The role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence. Circulation99(11), 1464–1470 (1999).
   PubMed Web of Science ®Google Scholar
• Gordon E, Panaghie G, Deng L et al. A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovasc. Res.77(1), 98–106 (2008).
   PubMed Web of Science ®Google Scholar
• Lehnart SE, Ackerman MJ, Benson DW Jr et al. Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affecting ion channel function. Circulation116(20), 2325–2345 (2007).
   PubMed Web of Science ®Google Scholar
• Bianchi L, Priori SG, Napolitano C et al. Mechanisms of IKs suppression in LQT1 mutants. Am. J. Physiol. Heart Circ. Physiol.279(6), H3003–H3011 (2000).
   Google Scholar
• Yamashita F, Horie M, Kubota T et al. Characterization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus. J. Mol. Cell. Cardiol.33(2), 197–207 (2001).
   PubMed Web of Science ®Google Scholar
• Gouas L, Bellocq C, Berthet M et al. New KCNQ1 mutations leading to haploinsufficiency in a general population: defective trafficking of a KvLQT1 mutant. Cardiovasc. Res.63(1), 60–68 (2004).
   PubMed Web of Science ®Google Scholar
• Aizawa Y, Ueda K, Wu L-m et al. Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect. FEBS Lett.574(1–3), 145–150 (2004).
   PubMed Web of Science ®Google Scholar
• Wilson AJ, Quinn KV, Graves FM, Bitner-Glindzicz M, Tinker A. Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovasc. Res.67(3), 476–486 (2005).
   PubMed Web of Science ®Google Scholar
• Sato A, Arimura T, Makita N et al. Novel mechanisms of trafficking defect caused by KCNQ1 mutations found in long QT syndrome. J. Biol. Chem.284(50), 35122–35133 (2009).
   PubMed Web of Science ®Google Scholar
• Labro AJ, Boulet IR, Timmermans J-P, Ottschytsch N, Snyders DJ. The rate-dependent biophysical properties of the LQT1 H258R mutant are counteracted by a dominant negative effect on channel trafficking. J. Mol. Cell. Cardiol.48(6), 1096–1104 (2009).
   PubMed Web of Science ®Google Scholar
• Ehrlich JR, Pourrier M, Weerapura M et al. KvLQT1 Modulates the distribution and biophysical properties of hERG. J. Biol. Chem.279(2), 1233–1241 (2004).
   PubMed Web of Science ®Google Scholar
• Biliczki P, Girmatsion Z, Brandes RP et al. Trafficking-deficient long QT syndrome mutation KCNQ1-T587M confers severe clinical phenotype by impairment of KCNH2 membrane localization: Evidence for clinically significant IKr-IKs [α]-subunit interaction. Heart Rhythm6(12), 1792–1801 (2009).
   PubMed Web of Science ®Google Scholar
• Bendahhou Sd, Donaldson MR, Plaster NM, Tristani-Firouzi M, Fu Y-H, Ptácek LJ. Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome. J. Biol. Chem.278(51), 51779–51785 (2003).
   PubMed Web of Science ®Google Scholar
• Soom M, Schönherr R, Kubo Y, Kirsch C, Klinger R, Heinemann SH. Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett.490(1–2), 49–53 (2001).
   PubMed Web of Science ®Google Scholar
• Choi B-O, Kim J, Suh BC et al. Mutations of KCNJ2 gene associated with Andersen-Tawil syndrome in Korean families. J. Hum. Genet.52(3), 280–283 (2007).
   PubMed Web of Science ®Google Scholar
• Ponce-Balbuena D, Lopez-Izquierdo A, Ferrer T, Rodriguez-Menchaca AA, Arechiga-Figueroa IA, Sanchez-Chapula JA. Tamoxifen inhibits inward rectifier K+ 2.x family of inward rectifier channels by interfering with phosphatidylinositol 4,5-bisphosphate-channel interactions. J. Pharmacol. Exp. Ther.331(2), 563–573 (2009).
   PubMed Web of Science ®Google Scholar
• Antzelevitch C, Pollevick GD, Cordeiro JM et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation115(4), 442–449 (2007).
   PubMed Web of Science ®Google Scholar
• Traverso M, Gazzerro E, Assereto S et al. Caveolin-3 T78M and T78K missense mutations lead to different phenotypes in vivo and in vitro. Lab. Invest.88(3), 275–283 (2008).
   PubMed Web of Science ®Google Scholar
• Mohler PJ, Schott J-J, Gramolini AO et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature421(6923), 634–639 (2003).
   PubMed Web of Science ®Google Scholar
• Nattel S. Therapeutic implications of atrial fibrillation mechanisms: can mechanistic insights be used to improve AF management? Cardiovasc. Res.54(2), 347–360 (2002).
   PubMed Web of Science ®Google Scholar
• Bellocq C, van Ginneken ACG, Bezzina CR et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation109(20), 2394–2397 (2004).
   PubMed Web of Science ®Google Scholar
• Brugada R, Hong K, Dumaine R et al. Sudden death associated with short-QT syndrome linked to mutations in hERG. Circulation109(1), 30–35 (2004).
   PubMed Web of Science ®Google Scholar
• Priori SG, Pandit SV, Rivolta I et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ. Res.96(7), 800–807 (2005).
   PubMed Web of Science ®Google Scholar
• Li G-R, Feng J, Yue L, Carrier M, Nattel S. Evidence for two components of delayed rectifier K+ current in human ventricular myocytes. Circ. Res.78(4), 689–696 (1996).
   PubMed Web of Science ®Google Scholar
• Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, Nerbonne JM. Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ. Res.80(6), 772–781 (1997).
   PubMed Web of Science ®Google Scholar
• Brundel BJJM, Van Gelder IC, Henning RH et al. Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels. J. Am. Coll. Cardiol.37(3), 926–932 (2001).
   PubMed Web of Science ®Google Scholar
• Olson TM, Alekseev AE, Liu XK et al. Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum. Mol. Genet.15(14), 2185–2191 (2006).
   PubMed Web of Science ®Google Scholar
• Yang Y, Li J, Lin X et al. Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation. J. Hum. Genet.54(5), 277–283 (2009).
   PubMed Web of Science ®Google Scholar
• Tanabe Y, Hatada K, Naito N et al. Over-expression of Kv1.5 in rat cardiomyocytes extremely shortens the duration of the action potential and causes rapid excitation. Biochem. Biophys. Res. Commun.345(3), 1116–1121 (2006).
   PubMed Web of Science ®Google Scholar
• Hong K, Piper DR, Diaz-Valdecantos A et al.De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc. Res.68(3), 433–440 (2005).
   PubMed Web of Science ®Google Scholar
• Roepke TK, Kontogeorgis A, Ovanez C et al. Targeted deletion of kcne2 impairs ventricular repolarization via disruption of I(K,slow1) and I(to,f). FASEB J.22(10), 3648–3660 (2008).
   PubMed Web of Science ®Google Scholar
• Li H, Guo W, Mellor RL, Nerbonne JM. KChIP2 modulates the cell surface expression of Kv1.5-encoded K+ channels. J. Mol. Cell. Cardiol.39(1), 121–132 (2005).
   PubMed Web of Science ®Google Scholar
• Eldstrom J, Choi WS, Steele DF, Fedida D. SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism. FEBS Lett.547(1–3), 205–211 (2003).
   PubMed Web of Science ®Google Scholar
• Folco EJ, Liu G-X, Koren G. Caveolin-3 and SAP97 form a scaffolding protein complex that regulates the voltage-gated potassium channel Kv1.5. Am. J. Physiol. Heart Circ. Physiol.287(2), H681–690 (2004).
   Google Scholar
• McEwen DP, Li Q, Jackson S, Jenkins PM, Martens JR. Caveolin regulates Kv1.5 trafficking to cholesterol-rich membrane microdomains. Mol. Pharmacol.73(3), 678–685 (2008).
   PubMed Web of Science ®Google Scholar
• Vatta M, Ackerman MJ, Ye B et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation114(20), 2104–2112 (2006).
   PubMed Web of Science ®Google Scholar
• Ye B, Balijepalli RC, Foell JD et al. Caveolin-3 associates with and affects the function of hyperpolarization-activated cyclic nucleotide-gated channel 4. Biochemistry47(47), 12312–12318 (2008).
   PubMed Web of Science ®Google Scholar
• Yang Z, Browning CF, Hallaq H et al. Four and a half LIM protein 1: a partner for KCNA5 in human atrium. Cardiovasc. Res.78(3), 449–457 (2008).
   PubMed Web of Science ®Google Scholar
• Holmes TC, Fadool DA, Ren R, Levitan IB. Association of src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science274(5295), 2089–2091 (1996).
   PubMed Web of Science ®Google Scholar
• Mason HS, Latten MJ, Godoy LD, Horowitz B, Kenyon JL. Modulation of Kv1.5 currents by protein kinase A, tyrosine kinase, and protein tyrosine phosphatase requires an intact cytoskeleton. Mol. Pharmacol.61(2), 285–293 (2002).
   PubMed Web of Science ®Google Scholar
• Zhang L, Foster K, Li Q, Martens JR. S-acylation regulates Kv1.5 channel surface expression. Am. J. Physiol. Cell Physiol.293(1), C152–C161 (2007).
   PubMed Web of Science ®Google Scholar
• Ebbing B, Mann K, Starosta A et al. Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Hum. Mol. Genet.,17(9), 1245–1252 (2008).
   PubMed Web of Science ®Google Scholar
• Schumacher SM, McEwen DP, Zhang L, Arendt KL, Van Genderen KM, Martens JR. Antiarrhythmic drug-induced internalization of the atrial-specific K+ channel Kv1.5. Circ. Res.104(12), 1390–1398 (2009).
   PubMed Web of Science ®Google Scholar
• Choi WS, Khurana A, Mathur R, Viswanathan V, Steele DF, Fedida D. Kv1.5 Surface expression is modulated by retrograde trafficking of newly endocytosed channels by the dynein motor. Circ. Res.97(4), 363–371 (2005).
   PubMed Web of Science ®Google Scholar
• Aquila LA, McCarthy PM, Smedira NG, Young JB, Moravec CS. Cytoskeletal structure and recovery in single human cardiac myocytes. J. Heart Lung Transplant.23(8), 954–963 (2004).
   PubMed Web of Science ®Google Scholar
• Furutani M, Trudeau MC, Hagiwara N et al. Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant hERG (G601S) potassium channel. Circulation99(17), 2290–2294 (1999).
   PubMed Web of Science ®Google Scholar
• Cordes JS, Sun Z, Lloyd DB et al. Pentamidine reduces hERG expression to prolong the QT interval. Br. J. Pharmacol.145(1), 15–23 (2005).
   PubMed Web of Science ®Google Scholar
• Guo J, Massaeli H, Li W et al. Identification of IKr and its trafficking disruption induced by probucol in cultured neonatal rat cardiomyocytes. J. Pharmacol. Exp. Ther.321(3), 911–920 (2007).
   PubMed Web of Science ®Google Scholar
• Aridor M, Hannan LA. Traffic jam: a compendium of human diseases that affect intracellular transport processes. Traffic1(11), 836–851 (2000).
   PubMed Web of Science ®Google Scholar
• Aridor M, Hannan LA. Traffic jams II: an update of diseases of intracellular transport. Traffic3(11), 781–790 (2002).
   PubMed Web of Science ®Google Scholar
• Delisle BP, Anson BD, Rajamani S, January CT. Biology of cardiac arrhythmias: ion channel protein trafficking. Circ. Res.94(11), 1418–1428 (2004).
   PubMed Web of Science ®Google Scholar
• Li J, Makrigiorgos GM. COLD-PCR: a new platform for highly improved mutation detection in cancer and genetic testing. Biochem. Soc. Trans.37(2), 427–432 (2009).
   PubMed Web of Science ®Google Scholar
• Pan N, Sun J, Lv C, Li H, Ding J. A hydrophobicity-dependent motif responsible for surface expression of cardiac potassium channel. Cell. Signal.21(2), 349–355 (2009).
   PubMed Web of Science ®Google Scholar
• Li W, Wang Q-f, Du R et al. Congenital long QT syndrome caused by the F275S KCNQ1 mutation: mechanism of impaired channel function. Biochem. Biophys. Res. Commun.380(1), 127–131 (2009).
   PubMed Web of Science ®Google Scholar
• Boulet IR, Raes AL, Ottschytsch N, Snyders DJ. Functional effects of a KCNQ1 mutation associated with the long QT syndrome. Cardiovasc. Res.70(3), 466–474 (2006).
   PubMed Web of Science ®Google Scholar
• Schmitt N, Calloe K, Nielsen NH et al. The novel C-terminal KCNQ1 mutation M520R alters protein trafficking. Biochem. Biophys. Res. Commun.358(1), 304–310 (2007).
   PubMed Web of Science ®Google Scholar
• Kanki H, Kupershmidt S, Yang T, Wells S, Roden DM. A structural requirement for processing the cardiac K+ channel KCNQ1. J. Biol. Chem.279(32), 33976–33983 (2004).
   PubMed Web of Science ®Google Scholar
• Teng S, Ma L, Dong Y et al. Clinical and electrophysiological characterization of a novel mutation R863X in hERG C-terminus associated with long QT syndrome. J. Mol. Med.82(3), 189–196 (2004).
   PubMed Web of Science ®Google Scholar
• Paulussen Ae, Raes A, Matthijs G, Snyders DJ, Cohen N, Aerssens J. A novel mutation (T65P) in the PAS domain of the human potassium channel hERG results in the long QT syndrome by trafficking deficiency. J. Biol. Chem.277(50), 48610–48616 (2002).
   PubMed Web of Science ®Google Scholar
• Keller D, Grenier J, Christ G et al. Characterization of novel KCNH2 mutations in type 2 long QT syndrome manifesting as seizures. Can. J. Cardiol.25(8), 455–462 (2009).
   PubMed Web of Science ®Google Scholar
• Huo J, Zhang Y, Huang N et al. The G604S-hERG mutation alters the biophysical properties and exerts a dominant-negative effect on expression of hERG channels in HEK293 cells. Pflügers Arch.456(5), 917–928 (2008).
   PubMed Web of Science ®Google Scholar
• Gong Q, Keeney DR, Robinson JC, Zhou Z. Defective assembly and trafficking of mutant hERG channels with C-terminal truncations in long QT syndrome. J. Mol. Cell. Cardiol.37(6), 1225–1233 (2004).
   PubMed Web of Science ®Google Scholar
• Hsueh C-H, Chen W-P, Lin J-L, Liu Y-B, Su M-J, Lai L-P. Functional studies on three novel HCNH2 mutations in Taiwan: identification of distinct mechanisms of channel defect and dissociation between glycosylation defect and assembly defect. Biochem. Biophys. Res. Commun.373(4), 572–578 (2008).
   PubMed Web of Science ®Google Scholar
• Gong Q, Zhang L, Moss AJ et al. A splice site mutation in hERG leads to cryptic splicing in human long QT syndrome. J. Mol. Cell. Cardiol.44(3), 502–509 (2008).
   PubMed Web of Science ®Google Scholar
• Paulussen ADC, Raes A, Jongbloed RJ et al.hERG mutation predicts short QT based on channel kinetics but causes long QT by heterotetrameric trafficking deficiency. Cardiovasc. Res.67(3), 467–475 (2005).
   PubMed Web of Science ®Google Scholar
• Christé G, Thériault O, Chahine M et al. A new C-terminal hERG mutation A915fs+47X associated with s ymptomatic LQT2 and auditory-trigger syncope. Heart Rhythm5(11), 1577–1586 (2008).
   PubMed Web of Science ®Google Scholar
• Sasano T, Ueda K, Orikabe M et al. Novel C-terminus frameshift mutation, 1122fs/147, of hERG in LQT2: additional amino acids generated by frameshift cause accelerated inactivation. J. Mol. Cell. Cardiol.37(6), 1205–1211 (2004).
   PubMed Web of Science ®Google Scholar
• Poelzing S, Forleo C, Samodell M et al. SCN5A polymorphism restores trafficking of a Brugada syndrome mutation on a separate gene. Circulation114(5), 368–376 (2006).
   PubMed Web of Science ®Google Scholar
• Pfahnl AE, Viswanathan PC, Weiss R et al. A sodium channel pore mutation causing Brugada syndrome. Heart Rhythm4(1), 46–53 (2007).
   PubMed Web of Science ®Google Scholar
• Mohler PJ, Rivolta I, Napolitano C et al. 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. USA101(50), 17533–17538 (2004).
   PubMed Web of Science ®Google Scholar
• Baroudi G, Acharfi S, Larouche C, Chahine M. Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. Circ. Res.90(1), e11–e16 (2002).
   PubMed Web of Science ®Google Scholar
• Makita N, Mochizuki N, Tsutsui H. Absence of a trafficking defect in R1232W/T1620M, a double SCN5A mutant responsible for Brugada syndrome. Circ. J.72(6), 1018–1019 (2008).
   PubMed Web of Science ®Google Scholar
• Tan B-H, Valdivia CR, Song C, Makielski JC. Partial expression defect for the SCN5A missense mutation G1406R depends on splice variant background Q1077 and rescue by mexiletine. Am. J. Physiol. Heart Circ Physiol.291(4), H1822–H1828 (2006).
   PubMed Web of Science ®Google Scholar
• Baroudi G, Pouliot V, Denjoy I, Guicheney P, Shrier A, Chahine M. Novel mechanism for Brugada syndrome: defective surface localization of an SCN5A mutant (R1432G). Circ. Res.88(12), e78–83 (2001).
   Web of Science ®Google Scholar
• Valdivia CR, Tester DJ, Rok BA et al. A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc. Res.62(1), 53–62 (2004).
   PubMed Web of Science ®Google Scholar
• Ye B, Valdivia CR, Ackerman MJ, Makielski JC. A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation. Physiol. Genomics12(3), 187–193 (2003).
   PubMed Web of Science ®Google Scholar
• Herfst LJ, Potet F, Bezzina CR et al. Na+ channel mutation leading to loss of function and non-progressive cardiac conduction defects. J. Mol. Cell. Cardiol.35(5), 549–557 (2003).
   PubMed Web of Science ®Google Scholar
• Hu D, Barajas-Martinez H, Nesterenko VV et al. Dual variation in SCN5A and CACNB2b underlies the development of cardiac conduction disease without Brugada syndrome. Pacing Clin. Electrophysiol.33(3), 274–285 (2010).
   PubMed Web of Science ®Google Scholar
• Valdivia CR, Medeiros-Domingo A, Ye B et al. Loss-of-function mutation of the SCN3B-encoded sodium channel {β}3 subunit associated with a case of idiopathic ventricular fibrillation. Cardiovasc. Res.86(3), 392–400 (2010).
   PubMed Web of Science ®Google Scholar
• London B, Michalec M, Mehdi H et al. Mutation in glycerol-3-phosphate dehydrogenase 1-like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation116(20), 2260–2268 (2007).
   PubMed Web of Science ®Google Scholar
• Krumerman A, Gao X, Bian J-S, Melman YF, Kagan A, McDonald TV. An LQT mutant minK alters KvLQT1 trafficking. Am. J. Physiol. Cell Physiol.286(6), C1453–1463 (2004).
   PubMed Web of Science ®Google Scholar
• Harmer SC, Wilson AJ, Aldridge R, Tinker A. Mechanisms of disease pathogenesis in long QT syndrome type 5. Am. J. Physiol. Cell Physiol.298(2), C263–273 (2009).
   Google Scholar
• Ballester LY, Benson DW, Wong B et al. Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome. Hum. Mutat.27(4), 388 (2006).
   PubMedGoogle Scholar
• Nof E, Luria D, Brass D et al. Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. Circulation116(5), 463–470 (2007).
   PubMedGoogle Scholar
• Ueda K, Nakamura K, Hayashi T et al. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J. Biol. Chem.279(26), 27194–27198 (2004).
   PubMed Web of Science ®Google Scholar