Faculty & Staff   

Building:Montreal Heart Institute
Room: S-4600
Phone: 514-376-3330 ext. 3990
Fax:514-376-1355

E-mail: stanley.nattel@icm-mhi.org
Web Site: http://www.medicine.mcgill.ca/pharma/snattel/

Research Area:

Research Description:

Dr Nattel’s area of research is basic mechanisms of cardiac electrical activity and arrhythmias, with a particular interest in cardiac ion channel function, atrial fibrillation and novel, mechanistically-based therapeutic approaches. Cardiac arrhythmias can interfere importantly with heart function and are the leading cause of sudden death in the population. Dr Nattel’s lab uses a wide range of models at the molecular, cellular, whole-animal and theoretical level to gain insights into clinically-relevant basic mechanisms and to identify novel therapeutic targets and candidates. Methodologies regularly used in the laboratory include Western blotting and immunochemistry for protein expression analysis; competitive RT-PCR and real-time PCR for gene expression studies; co-expression and co-immunoprecipitation for protein interaction analysis; cloning and site-directed mutagenesis to identify novel genes and study structure-function relationships, promoter analysis for studies of gene expression regulation mechanisms; patch clamp studies of isolated cardiac cells, mammalian cell lines and Xenopus oocytes for studies of ion channel function; animal models of cardiac disease to study remodeling and arrhythmia mechanisms; high-density extracellular electrode and optical mapping to study arrhythmia mechanisms; and parallel-processor computation of mathematical models to evaluate theoretical concepts.

Selected Publications:

Qi XY, Yeh YH, Xiao L, Burstein B, Maguy A, Chartier D, Villeneuve LR, Brundel BJJM, Dobrev D, Nattel S: Cellular signalling underlying atrial tachycardia remodeling of L-type calcium-current. Circ Res 103: 845-854, 2008.

Xiao L, Coutu P, Villeneuve LR, Maguy A, Le Bouter S, Allen BG, Nattel S : Mechanisms underlying rate-dependent remodeling of transient outward potassium current in canine ventricular myocytes. Circ Res 103: 733-742, 2008.

Xiao L, Xiao J, Luo X, Lin H, Wang Z, Nattel S: Feedback remodeling of cardiac potassium current expression: a novel potential mechanism for control of repolarization reserve. Circulation 118: 983-992, 2008.

Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JMO, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH, Lambert J, Le Heuzey J-Y, O’Hara G, Pedersen OD, Rouleau J-L, Singh BN, Warner Stevenson L, Stevenson WG, Thibault B, Waldo AL : A multicenter randomized trial of rhythm-control versus rate-control in patients with atrial fibrillation and congestive heart failure. N Engl J Med 358: 2667-77, 2008.

Burstein B, Libby E, Calderone A, Nattel S: Differential behaviors of atrial versus ventricular fibroblasts. A potential role for platelet-derived growth factor in atrial-ventricular remodeling differences. Circulation 117: 1630-1641, 2008.

Lemola K, Chartier D, Yeh YH, Dubuc M, Cartier R, Armour A, Ting M, Sakabe M, Shiroshita-Takeshita A, Comtois P, Nattel S: Pulmonary vein region ablation in experimental vagal atrial fibrillation: Role of pulmonary veins versus autonomic ganglia. Circulation 117: 470-477, 2008.

Sakabe M, Shiroshita-Takeshita A, Maguy A, Dumesnil C, Nigam A, Leung TK, Nattel S: Omega-3 polyunsaturated fatty acids prevent atrial fibrillation associated with heart failure but not atrial tachycardia remodeling. Circulation 116: 2101-2109, 2007.

Nattel S, Maguy A, Le Bouter S, Yeh Y-H: Arrhythmogenic ion-channel remodeling in the heart: Heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev 87: 425-456, 2007.

Cardin S, Libby E, Pelletier P, Le Bouter S, Shiroshita-Takeshita A, Le Meur N, Léger J, Demolombe S, Ponton A, Glass L, Nattel S: Contrasting gene expression profiles in two canine models of atrial fibrillation. Circ Res 100: 425-433, 2007.

Shiroshita-Takeshita A, Sakabe M, Haugan K, Hennan JK, Nattel S: Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs. Circulation 115: 310-318, 2007.

Brundel BJJM, Shiroshita-Takeshita A, Qi XY, Yeh Y-H, Chartier D, van Gelder IC, Henning RH, Kampinga HH, Nattel S: Induction of heat shock response protects the heart against atrial fibrillation. Circ Res 99: 1394-1402, 2006.

Nattel S, Carlsson L: Innovative approaches to anti-arrhythmic drug therapy. Nat Rev Drug Discov 5: 1034-1049, 2006.

Cha TJ, Ehrlich JR, Chartier D, Xiao L, Nattel S: Kir3-based inward rectifier potassium current: potential role in atrial tachycardia remodeling effects on atrial repolarization and arrhythmias. Circulation 113: 1730-1737, 2006.

Tsuji Y, Zicha S, Qi XY, Kodama I, Nattel S: Potassium channel subunit remodeling in rabbits exposed to long-term bradycardia or tachycardia: Discrete arrhythmogenic consequences related to differential delayed-rectifier changes. Circulation 113: 345-355, 2006.

Nattel S, Opie LH: Controversies in atrial fibrillation. Lancet 367: 262-272, 2006.

Kneller J, Kalifa J, Zou R, Zaitsev AV, Warren M, Berenfeld O, Vigmond EJ, Leon LJ, Nattel S, Jalife J: Mechanisms of AF termination by pure sodium channel blockade in an ionically-realistic mathematical model. Circ Res 96: e48-e57, 2005.

Shiroshita-Takeshita A, Schram G, Lavoie J, Nattel S: The effect of simvastatin and antioxidant vitamins on atrial fibrillation-promotion by atrial tachycardia remodeling in dogs. Circulation 110: 2313-2319, 2004.

Ehrlich JR, Pourrier M, Weerapura M, Éthier N, Marmabachi AM, Hébert TE, Nattel S: KvLQT1 modulates the distribution and biophysical properties of HERG: A novel alpha-subunit interaction between delayed rectifier currents. J Biol Chem 279: 1233-1241, 2004.

Cha TJ, Ehrlich JR, Zhang L, Shi YF, Tardif JC, Leung TK, Nattel S: Dissociation between ionic remodeling and ability to sustain atrial fibrillation during recovery from experimental congestive heart failure. Circulation 109: 412-418, 2004.

Nattel S. Lost anchors cost lives. Nature 421: 587-590, 2003.

Kalifa J, Jalife J, Zaitsev AV, Bagwe S, Warren M, Moreno J, Berenfeld O, Nattel S: Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation. Circulation 108: 668-671, 2003.

Pourrier M, Zicha S, Han W, Nattel S: Canine ventricular KCNE2 expression resides predominantly in Purkinje fibers. Circ Res 93: 189-191, 2003.

Caballero R, Pourrier M, Schram G, Delpon E, Tamargo J, Nattel S: Effects of flecainide and quinidine on Kv4.2 currents: Voltage dependence and role of S6 valines. Br J Pharmacol 138: 1475-1484, 2003.

Shinagawa K, Shiroshita-Takeshita A, Schram G, Nattel S: Effects of antiarrhythmic drugs on fibrillation in the remodeled atrium: Insights into the mechanism of the superior efficacy of amiodarone. Circulation 107: 1440-1446, 2003.

Sinno H, Derakhchan K, Libersan D, Merhi Y, Leung TK, Nattel S: Atrial ischemia promotes atrial fibrillation in dogs. Circulation 107: 1930-1936, 2003.

Han W, Bao W, Wang Z, Nattel S: Comparison of ion-channel subunit expression in canine cardiac Purkinje fibers and ventricular muscle. Circ Res 91: 790-797, 2002.

Shinagawa K, Shi Y-F, Tardif JC, Leung T-K, Nattel S: Dynamic nature of atrial fibrillation substrate during development and reversal of heart failure in dogs. Circulation 105: 2672‑2678, 2002.

Kneller J, Zou R, Vigmond EJ, Wang Z, Leon LJ, Nattel S: Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties. Circ Res 90: E73-E87, 2002.

Nattel S: New ideas about atrial fibrillation 50 years on. Nature 415: 219-226, 2002.

Li D, Shinagawa K, Pang L, Leung TK, Cardin S, Wang Z, Nattel S: Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation 104: 2608-2614, 2001.

Han W, Chartier D, Li D, Nattel S: Ionic remodeling of cardiac Purkinje cells by congestive heart failure. Circulation 104: 2095-2100, 2001.

Li D, Zhang L, Kneller J, Nattel S: Potential ionic mechanism for repolarization differences between canine right and left atrium. Circ Res 88: 1168-1175, 2001.

Li D, Benardeau A, Nattel S: Contrasting efficacy of dofetilide in differing experimental models of atrial fibrillation. Circulation 102: 104-112, 2000.

Li D, Melnyk P, Feng J, Wang Z, Petrecca K, Shrier A, Nattel S: Effects of experimental heart failure on atrial cellular and ionic electrophysiology. Circulation 101: 2631-2638, 2000.

Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J, Dubuc M, Gagné P, Nattel S, Thibault B: Amiodarone to prevent recurrence of atrial fibrillation. N Engl J Med 342: 913-920, 2000.