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1 Cardiac Rhythm Management Lab and Department of Biomedical Engineering, University of Alabama-Birmingham, Birmingham, Alabama 35294; 2 Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana 70125; 3 Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112; and 4 Department of Physiology and Biophysics, University of Calgary School of Medicine, Calgary, Alberta, Canada T2N 4N1
Purkinje-ventricular junctions (PVJs) have been
implicated as potential sites of arrhythmogenesis, in part because of
the dispersion of action potential duration (APD) between Purkinje (P)
and ventricular (V) myocytes. To characterize electrotonic modulation
of APD as a function of junctional resistance
(Rj), we
coupled single isolated rabbit P and V myocytes with an electronic circuit. In seven of eight PV myocyte pairs, both APDs shortened on
coupling at Rj = 50 M
. This was in contrast to modulation of APD in paired
ventricular myocytes, which demonstrated APD shortening of the
intrinsically longer action potential and APD prolongation of the
intrinsically shorter action potential. Companion computer simulations,
performed to suggest possible mechanisms for the paradoxical shortening
of the V action potential in paired P and V myocytes, showed that the
difference in intrinsic peak plateau potentials
(Vpp) of the P
and V myocytes determined whether the V action potential shortened or
prolonged on coupling. This difference in
Vpp caused a
large, repolarizing coupling current to flow to the V myocyte,
contributing to early inactivation of the L-type calcium current and
early activation of the inward rectifier current. These results suggest
that intrinsic differences in phase 1 repolarization could yield
differing patterns of APD shortening or prolongation in the network of
subendocardial PVJs, leaving some PVJs vulnerable to conduction of
premature stimuli while other PVJs remain refractory.
coupling clamp circuit; membrane models; transient outward current
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