F A C U L T Y P R O F I L E
Boyden, Penelope A. Ph.D.
Cardiac electrophysiology; mechanisms of arrhythmias in experimental and naturally occurring animal models of disease
Office: Physicians and Surgeons | 7th floor | Room 464
Cardiac electrophysiology; mechanisms of arrhythmias in experimental and naturally occurring animal models of disease.
Research in our laboratory is dedicated to determining the electrophysiological basis of abnormal heart rhythms (cardiac arrhythmias). In one set of projects we enzymatically isolate single cells from hearts that have become arrhythmic due to experimental myocardial infarction, or pacing induced atrial fibrillation. We examine the function of specific ionic currents, in particular the sodium and potassium currents in the diseased cells and how this might be altered by drugs.
In other groups of experiments we use single cells from diseased hearts in order to determine how intracelluar calcium homeostasis is altered in cells of hearts post myocardial infarction. In some studies we combine whole cell voltage clamp
techniques with epifluorescent and Ca2+ imaging techniques. We have found examples of reverse excitation contraction coupling where cytosolic Ca2+ elicits nondriven electrical activity (see www.cvr.ucalgary.ca/slideshow for movie example). By studying whole heart and single cell electrophysiology of diseased hearts we can better understand how antiarrhythmic drugs work to terminate and/or prevent cardiac arrhythmias.
1. Boyden PA, Barbhaiya C, Lee T, terKeurs HEDJ. (2003) Nonuniform Ca2+ Transients in arrhythmogenic Purkinje cells that survive in the infarcted canine heart. Cardiovascular Research 57:681-693
2. Boyden PA, Dun W, Barbhaiya C, terKeurs HEDJ. (2004) 2APB and JTV519(K201) sensitive micro Ca2+ transients and cell-wide Ca2+ waves in arrhythmogenic Purkinje cells that survive in the infarcted heart. Heart Rhythm 1:2180-2226
3. Wakayama Y, Miura M, Stuyvers BD, Boyden PA, ter Keurs HEDJ. (2005) Spatial Non-uniformity of Excitation-Contraction Coupling Causes Arrhythmogenic Ca2+ Waves in Rat Cardiac Muscle. Circulation Research 96:1266-1273
4. Stuyvers BD, Dun W, Matkovich S, Sorrentino V, Boyden PA, ter Keurs HEDJ. (2005) Confocal Analysis of Ca2+ Sparks and Waves in Canine Purkinje Cells; A Triple Layered System of Activation. Circulation Research 97:35-43
5. Baba S, Dun W, Cabo C, Boyden PA. (2005) Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. Circulation 112:2386-2396
6. Baba S, Dun W, Hirose M, Boyden PA. (2006) Sodium current function in adult and aged canine atrial cells. AJP 291:H756-H761
7. Cabo C, Boyden PA. 2006. Heterogeneous Gap Junction Remodeling Stabilizes Reentrant Circuits in the Epicardial Border Zone of the Healing Canine Infarct: A Computational Study. AJP; ;291(6):H2606-16
8. Hirose M, Stuyvers B, Dun W, ter Keurs HEDJ and PA Boyden.2008.Wide Long lasting Perinuclear Ca2+ Release Events Generated by an Interaction between Ryanodine and IP3 Receptors in Canine Purkinje Cell. JMCC 45: 176-184
9. Cabo C, Boyden PA. 2009. The extracellular Space attenuates the effect of Gap junction Remodeling on Wave Propagation. A Computational Story. Biophys J. 96: 3092–3101
10. Hirose M, Stuyvers B, Dun W, ter Keurs HEDJ and PA Boyden. 2008. Function of Ca2+ release Channels in Purkinje cells that survive in the Infarcted Canine Heart; a Mechanism for triggered Ventricular beats. Circ: Arrhythmia and Electrophysiology 1: 387-395
11. John S. Lowe1, Oleg Palygin2, Naina Bhasin1, Thomas J. Hund1, P A. Boyden3, Erwin Shibata2, Mark E. Anderson1,2, and Peter J. Mohler1,2:V.2008.Voltage-gated Nav channel targeting in heart requires an ankyrin-G-dependent cellular pathway .JCB 14;180(1):173-86
12. Hund TJ, Wright P, Dun W, Boyden PA, Mohler PJ. 2009. Remodeling of ankyrin-B following myocardial infarction. Cardiovasc Res. Mar 1;81(4):742-9.
13. Macia E and Boyden PA. Stem Cell Therapy Is Proarrhythmic? 2009. Circulation 119:1814-1823
14. Boyden PA, M Hirose and W Dun. Cell to Bedside; Cardiac Purkinje cells. 2010. Heart Rhythm 7; 127-135. PMID: 19939742
15. Pallante BA, Giovannone S, Fang-Yu L, Zhang J, Liu N, Kang G, Dun W, Boyden PA, Fishman GI.Contactin-2 expression in the cardiac Purkinje fiber network. 2010. Circ Arrhythm Electrophysiol. 1;3(2):186-94. PMID: 20110552
16. Gudmundsson H, Hund TJ, Wright PJ, Kline CF, Snyder JS, Qian L, Koval OM, Cunha SR, George M, Rainey MA, Kashef FE, Dun W, Boyden PA, Anderson ME, Band H, Mohler PJ.2010. EH Domain Proteins Regulate Cardiac Membrane Protein Targeting. Circ Res;107(1):84-95
17. Miura M, Nishio T, Hattori T, Murai N, Stuyvers BD, Shindoh C, Boyden PA. 2010. Effect of non uniform muscle contraction on sustainability and frequency of triggered arrhythmias in rat cardiac muscle. Circ Arrhythm Electrophysiol. 2010; 121: 2711-2717
18. Lee YS, Dun W, Boyden PA, Sobie E.2011 Complex and rate dependent beat-to-beat variations in Ca transients of canine Purkinje cells. JMCC. 50(4):662
19. Macia E, Dolmatova E, Cabo C, Shvilkina T, Dun W, Coromilas J, Ciaccio E, Boyden PA, Wit AL, Duffy HS.2011. Characterization of Gap Junction Remodeling in the EBZ of Healing Canine Infarcts and Electrophysiological Effects of Partial Reversal by Rotigaptide. Circ Arrhythm Electrophysiol 4: 344-351
20. Liu N, Denegri M, Ruan Y, Avelino-Cruz JE,Perissi A, Negri S,Napolitano C, Coetzee WA, Boyden PA, Priori SG. 2011. Flecainide exerts an Antiarrhythmic effect in a mouse model of CPVT by Increasing the Threshold for Triggered Activity. Circ Res. 109; online