Page 79 - Cardiac Electrophysiology | A Modeling and Imaging Approach

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intercellular coupling is reduced, the

discontinuous nature of conduction is revealed
in the electrogram. Because of the long delays
at gap junctions, depolarizations of neighbor-

ing cells are more separated in time, giving rise
to distinct deflections in the electrogram
waveform.

Scaling and Higher Dimensionality. The

principles of discontinuous conduction were
established above for action potential
propagation at the cellular (microscopic) scale.

These principles can be scaled to structural
discontinuities on a more global (macroscopic)
scale. Each excitable element (a single cell in
the microscopic simulations) can be
considered to represent a tightly-coupled

group of cells (fiber bundle) separated from Figure 3.4. Relationship between the upstroke
neighboring bundles by connective tissue, of a propagating AP (V ) and extracellular
m
except at discrete sites of coupling. Such unipolar electrograms (ϕ ). A. Normal
e
inhomogeneous substrate is characteristic intercellular coupling. B. Coupling is reduced
by a factor of 50; 1 and 2 indicate irregularities
of aging cardiac tissue and of infracted in the electrogram waveform, reflecting
myocardium. In reference to Figure 3.4, depolarization of individual cells. Adapted
multi-deflection “fractionated” electrograms from Rudy and Quan [180], with permission
from John Wiley and Sons.
are indeed recorded in these settings. 185,191,192

The principles and mechanisms of discontinuous conduction, established in 1-dimensional
models, apply to higher (two and three) spatial dimensions as well. However, quantitative

differences do exist because of different patterns of cell –to-cell connectivity. In a 1-dimensional
strand (only longitudinal gap junctions are present at cell ends) with normal gap junction
coupling, conduction delay across the gap junction equals conduction time across the entire cell
and constitutes 50% of the total conduction time. The presence of lateral intercellular connections
in higher dimensions was shown to reduce cell-to-cell delay to about 20% of total conduction time

in tissue with normal gap junction coupling. 193

Other Complexities. In most simulations of discontinuous conduction, the gap junctions are

represented as purely conductive pathways, characterized by static resistance which does not
vary during the passage of the action potential. Voltage clamp experiments in cell pairs revealed
dynamic properties of the gap junction conductance. Simulations of conduction in presence of
the gap junction dynamics showed that this property has a small effect, only when cells are
partially uncoupled .
194