Inhibition of late sodium current by mexiletine: A novel pharmotherapeutical approach in timothy syndrome

Circulation: Arrhythmia and Electrophysiology

Volumn 6, Issue 3, 2013, Pages 614-622

  Gao, Yuanfeng ^a   Xue, Xiaolin ^b   Hu, Dayi ^a   Liu, Wenling ^a   Yuan, Yue ^c   Sun, Hongmei ^b   Li, Lei ^a   Timothy, Katherine W ^d   Zhang, Li ^d   Li, Cuilan ^a   Yan, Gan Xin ^b,d  

^a PEKING UNIVERSITY PEOPLE S HOSPITAL   (China)

^b THE FIRST AFFILIATED HOSPITAL OF XI AN JIAOTONG UNIVERSITY   (China)

^c CAPITAL MEDICAL UNIVERSITY   (China)

^d LANKENAU INSTITUTE FOR MEDICAL RESEARCH   (United States)

Author keywords

Atrioventricular block; Late sodium current; LQT8; Mexiletine; T wave alternans; Timothy syndrome

Indexed keywords

MEXILETINE; SODIUM CHANNEL; VOLTAGE GATED SODIUM CHANNEL BLOCKING AGENT;

ARTICLE; ATRIOVENTRICULAR BLOCK; CASE REPORT; CHILD; CHINESE; CLONING; ELECTROCARDIOGRAM; FEMALE; GENETIC SCREENING; HOLTER MONITORING; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; LANGUAGE DELAY; LEUKOCYTE; LONG QT SYNDROME; MOSAICISM; MOUTH MUCOSA; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRESCHOOL CHILD; PRIORITY JOURNAL; QT PROLONGATION; SODIUM CURRENT; SPERM; SYNDACTYLY; T WAVE; THERAPY EFFECT; TIMOTHY SYNDROME; ANIMAL; ANIMAL MODEL; DOPPLER ECHOCARDIOGRAPHY; DRUG EFFECT; ELECTROCARDIOGRAPHY; FOLLOW UP; GENE EXPRESSION REGULATION; GENETIC ASSOCIATION; GENETICS; LATE SODIUM CURRENT; LQT8; METHODOLOGY; MUSCLE CELL; RABBIT; REVIEW; SEVERITY OF ILLNESS INDEX; T WAVE ALTERNANS; TREATMENT OUTCOME;

ATRIOVENTRICULAR BLOCK; LATE SODIUM CURRENT; LQT8; MEXILETINE; T WAVE ALTERNANS; TIMOTHY SYNDROME;

ANIMALS; CHILD, PRESCHOOL; DNA MUTATIONAL ANALYSIS; ECHOCARDIOGRAPHY, DOPPLER; ELECTROCARDIOGRAPHY; ELECTROCARDIOGRAPHY, AMBULATORY; FEMALE; FOLLOW-UP STUDIES; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENETIC ASSOCIATION STUDIES; GENETIC TESTING; HUMANS; LONG QT SYNDROME; MEXILETINE; MODELS, ANIMAL; MUSCLE CELLS; RABBITS; SEVERITY OF ILLNESS INDEX; SODIUM CHANNELS; SYNDACTYLY; TREATMENT OUTCOME; VOLTAGE-GATED SODIUM CHANNEL BLOCKERS;

EID: 84883013207     PISSN: 19413149     EISSN: 19413084     Source Type: Journal    
DOI: 10.1161/CIRCEP.113.000092     Document Type: Article

References (27)

1. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119:19-31.
2. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A. 2005;102:8089-8096; discussion 8086.
3. Yarotskyy V, Gao G, Peterson BZ, Elmslie KS. The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. J Physiol. 2009;587:551-565.
4. Sicouri S, Timothy KW, Zygmunt AC, Glass A, Goodrow RJ, Belardinelli L, Antzelevitch C. Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of ranolazine. Heart Rhythm. 2007;4:638-647.
5. Shah DP, Baez-Escudero JL, Weisberg IL, Beshai JF, Burke MC. Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). Pacing Clin Electrophysiol. 2012;35:e62-e64.
6. Jacobs A, Knight BP, McDonald KT, Burke MC. Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). Heart Rhythm. 2006;3:967-970.
7. Guo D, Lian J, Liu T, Cox R, Margulies KB, Kowey PR, Yan GX. Contribution of late sodium current (I(Na-L)) to rate adaptation of ventricular repolarization and reverse use-dependence of QT-prolonging agents. Heart Rhythm. 2011;8:762-769.
8. Liu T, Brown BS, Wu Y, Antzelevitch C, Kowey PR, Yan GX. Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias. Heart Rhythm. 2006;3:948-956.
9. Wu L, Guo D, Li H, Hackett J, Yan GX, Jiao Z, Antzelevitch C, Shryock JC, Belardinelli L. Role of late sodium current in modulating the proarrhythmic and antiarrhythmic effects of quinidine. Heart Rhythm. 2008;5:1726-1734.
10. Guo D, Zhou J, Zhao X, Gupta P, Martin J, Kowey PR, Wu Y, Liu T, Yan GX. Calcium channel recovery kinetics versus ventricular repolarization: Preserved membrane-stabilizing mechanism across species. Heart Rhythm. 2008;5:271-279.
11. Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME. Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc. 2003;78:1479-1487.
12. Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE. Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature. 2011;471:230-234.
13. Etheridge SP, Bowles NE, Arrington CB, Pilcher T, Rope A, Wilde AA, Alders M, Saarel EV, Tavernier R, Timothy KW, Tristani-Firouzi M. Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. Am J Med. Genet A. 2011;155A:2578-2583.
14. Krause U, Gravenhorst V, Kriebel T, Ruschewski W, Paul T. A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). Clin Res Cardiol. 2011;100:1123-1127.
15. Gillis J, Burashnikov E, Antzelevitch C, Blaser S, Gross G, Turner L, Babul-Hirji R, Chitayat D. Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. Am J Med. Genet A. 2012;158A:182-187.
16. Youssoufian H, Pyeritz RE. Mechanisms and consequences of somatic mosaicism in humans. Nat Rev Genet. 2002;3:748-758.
17. Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol. 2010;3:401-408.
18. Sun Y, Quan XQ, Fromme S, Cox RH, Zhang P, Zhang L, Guo D, Guo J, Patel C, Kowey PR, Yan GX. A novel mutation in the KCNH2 gene associated with short QT syndrome. J Mol Cell Cardiol. 2011;50: 433-441.
19. Chockalingam P, Crotti L, Girardengo G, Johnson JN, Harris KM, van der Heijden JF, Hauer RN, Beckmann BM, Spazzolini C, Rordorf R, Rydberg A, Clur SA, Fischer M, van den Heuvel F, Kääb S, Blom NA, Ackerman MJ, Schwartz PJ, Wilde AA. Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol. 2012;60:2092-2099.
20. Bankston JR, Kass RS. Molecular determinants of local anesthetic action of beta-blocking drugs: implications for therapeutic management of long QT syndrome variant 3. J Mol Cell Cardiol. 2010;48:246-253.
21. Pine M, Favrot L, Smith S, McDonald K, Chidsey CA. Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris. Circulation. 1975;52:886-893.
22. Mullane JF, Kaufman J, Dvornik D, Coelho J. Propranolol dosage, plasma concentration, and beta blockade. Clin Pharmacol Ther. 1982;32:692-700.
23. Noda T, Takaki H, Kurita T, Suyama K, Nagaya N, Taguchi A, Aihara N, Kamakura S, Sunagawa K, Nakamura K, Ohe T, Horie M, Napolitano C, Towbin JA, Priori SG, Shimizu W. Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome. Eur Heart J. 2002;23:975-983.
24. Nathan AT, Antzelevitch C, Montenegro LM, Vetter VL. Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. Anesthesiology. 2012;117:1117-1126.
25. Jia S, Lian J, Guo D, Xue X, Patel C, Yang L, Yuan Z, Ma A, Yan GX. Modulation of the late sodium current by ATX-II and ranolazine affects the reverse use-dependence and proarrhythmic liability of IKr blockade. Br J Pharmacol. 2011;164:308-316.
26. Shimizu W. T wave alternans: from cell to clinical. J Cardiovasc Electrophysiol. 2001;12:428-430.
27. Guo D, Young L, Patel C, Jiao Z, Wu Y, Liu T, Kowey PR, Yan GX. Calcium-activated chloride current contributes to action potential alternations in left ventricular hypertrophy rabbit. Am J Physiol Heart Circ Physiol. 2008;295:H97-H104.