pab4@columbia.edu

PROFESSOR OF PHARMACOLOGY

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 or pairs of 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.  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.

Selected Publications:

1. Boyden PA, Pu J, Pinto J and ter Keurs HEDJ: Ca²⁺ transients and Ca²⁺ waves in Purkinje cells: Role in action potential initiation. Circ. Res. 86:448-455, 2000. Abstract PDF file

2. Boyden PA, Barbhaiya C, Lee T and ter Keurs HEDJ: Nonuniform Ca²⁺ transients in arrhythmogenic Purkinje cells that survive in the infarcted heart. Cardiovasc. Res. 57:681-693, 2003. Abstract PDF File

3. Cabo C and Boyden PA: Electrical remodeling of the epicardial border zone in the canine infarcted heart: A computational analysis. Am. J. Physiol. 284:H372-H384, 2003. Abstract PDF File

4. Yao JA, Hussain W, Patel P, Peters NS, Boyden PA and Wit AL: Remodeling of gap junctional channel function in epicardial border zone of healing canine infarcts. Circ. Res. 92:437-443, 2003. Abstract PDF file

5. Dun W, Chandra P, Danilo P Jr, Rosen MR and Boyden PA: Chronic atrial fibrillation does not further decrease outward currents. It increases them. Am. J. Physiol. Heart Circ. Physiol. 285:H1378-H1384, 2003. Abstract PDF File

6. Dun W, Baba S, Yagi T and Boyden PA: Dynamic remodeling of K⁺ and Ca²⁺ currents in cells that survived in the epicardial border zone of the canine healed infarcted heart. Am. J. Physiol. Heart Circ. Physiol. 287:H1046-H1054, 2004. Abstract PDF File

7. Davidoff AW, Boyden PA, Schwartz K, Michel JB, Zhang YM, Obayashi M, Crabbe D and ter Keurs HEDJ: Congestive heart failure after myocardial infarction in the rat: Cardiac force and spontaneous sarcomere activity. Ann. N.Y. Acad. Sci. 1015:84-95, 2004. Abstract PDF File

8. Wakayama Y, Miura M, Stuyvers BD, Boyden PA and ter Keurs HEDJ: Spatial nonuniformity of excitation-contraction coupling causes arrhythmogenic Ca²⁺ waves in rat cardiac muscle. Circ. Res. 96:1266-1273, 2005. Abstract PDF File

9. Stuyvers BD, Dun W, Matkovich S, Sorrentino V, Boyden PA and ter Keurs HEDJ: Ca²⁺ sparks and waves in canine purkinje cells: A triple layered system of Ca²⁺ activation. Circ. Res. 97:35-43, 2005. Abstract PDF File

10. Baba S, Dun W, Cabo C and Boyden PA: Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. Circulation 112:2386-2396, 2005. Abstract PDF File

Purkinje cells survive in the infarcted heart and become the foci of ventricular arrhythmias. The images in this figure depict the spatial and temporal changes of subcellular Ca2+ in a cell aggregate. Images were acquired at 30 frames/s and time in the sequence is denoted in white. The intensity of the fluorescence indicates the level of intracellular Ca2+. In this aggregate, two micro-Ca2+ transients secondary to spontaneous Ca2+ release appear at 66 ms and travel as meandering Ca2+ waves. At 528 ms, the micro-Ca2+ waves appear to coalesce and form a larger cell-wide Ca2+ wave which then propagates the length of the aggregate. Other studies show that these large cell-wide Ca2+ waves cause membrane depolarizations and action potentials.