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Penelope A. Boyden, Ph.D.
Professor of Pharmacology in the Center for Molecular Therapeutics
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Research
Summary
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.
http://www.cumc.columbia.edu/dept/cmt/participants/bios/boyden.shtml
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Selected Publications:
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-H2616
8. Hirose M, Stuyvers B, Dun W, ter Keurs HEDJ, Boyden PA. (2008) Wide Long lasting Perinuclear Ca2+ Release Events Generated by an Interaction between Ryanodine and IP3 Receptors in Canine Purkinje Cell. JMCC
:In Press
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