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Am J Physiol Heart Circ Physiol 281: H533-H542, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 2, H533-H542, August 2001

Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation

Fadi G. Akar1, Bradley J. Roth2, and David S. Rosenbaum1

1 Heart and Vascular Research Center and Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998; and 2 Department of Physics, Oakland University, Rochester, Michigan 48309

Electrical coupling between myocytes plays a critical role in propagation, repolarization, and arrhythmias. On the basis of predictions from cable theory, we hypothesized that the cardiac space constant (lambda ) measured from the decay of subthreshold transmembrane potential (ST-Vm) in space would provide an index of regional cell-to-cell coupling in the intact heart. With the use of voltage-sensitive dyes, the distribution of ST-Vm was measured from hundreds of sites in close proximity to the site of subthreshold stimulation. lambda  was calculated from the exponential decay of ST-Vm in space. Consistent with known directional differences in axial resistance, the spatial distribution of ST-Vm was strongly dependent on fiber orientation, because lambda  was significantly (P < 0.001) longer along (1.5 ± 0.1 mm) compared with across (0.8 ± 0.1 mm) fibers. There was a close linear relationship (P < 0.001) between conduction velocity (CV) and lambda  along all fiber angles tested. Reducing gap junctional conductance by heptanol reversibly decreased CV and lambda  in parallel by ~50%. In contrast, sodium channel blockade by flecainide slowed CV by 40% but had no effect on lambda , reaffirming that lambda  was an index of passive but not active membrane properties. These data establish the feasibility of measuring lambda  as an index of cell-to-cell coupling in the intact heart, and indicate strong dependency of lambda  on fiber orientation and pharmacological alterations of gap junction conductance.

space constant; gap junctions; optical mapping; arrhythmias


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