Page 85 - YORAM RUDY BOOK FINAL

P. 85
Role of Tissue Structure in Action Potential Propagation

As stated earlier, cardiac conduction is the result of an interplay between membrane
factors (source) and tissue structural factors (sink). The previous section focused on the
membrane and its excitability properties. Here we examine the effects of tissue structural

properties on conduction. In particular, we focus on reduced cell to cell coupling at gap junctions,
and on structural inhomogeneities that alter source-sink relationships in a spatially dependent
manner (e.g. tissue expansion or branching).

Reduced Gap Junction Coupling

The previous section characterized the properties of slow conduction due to reduced
membrane excitability. Another mechanism of slow conduction is reduced intercellular coupling

due to reduced gap junction conductance. Figure 3.8 shows conduction velocity (solid line) and
SF (dashed line) as a function of gap junction conductance. The simulation was conducted in the
1-dimensional fiber by reducing the conductance of all gap junctions uniformly over a range.
Similar to reduced membrane excitability, progressive reduction of intercellular coupling slows

conduction in a monotonic fashion. However, conduction attains a much slower velocity before
failure occurs (0.26 cm/sec due to reduced coupling, compared to 17 cm/sec due to reduced
membrane excitability). Relative to normal conduction, reduced coupling can decrease velocity by
a factor of 200, while it is only a factor of 3 for reduced excitability. The extremely slow minimum

velocity in Figure 3.8 corresponds closely to that measured experimentally in synthetic strands of
decoupled rat myocytes. 178

The explanation to this large difference between membrane supported and gap-junction

supported slow conduction lies in the strikingly different behavior of SF (compare Figure 3.8 and
Figure 3.5). In contrast to the monotonic decrease with decreasing excitability (Figure 3.5), SF in
Figure 3.8 increases to a maximum as coupling is reduced. This maximum is reached at a highly
reduced level of gap junction coupling of 0.023μS, about 100-fold smaller than normal coupling

of 2.5 μS. The conduction velocity at maximum SF is very slow, about 1/15 of normal velocity.
Hence, slow conduction due to reduced gap junction coupling is very robust, safer than
normal conduction. This seemingly paradoxical property is a manifestation of the increased
discontinuous nature of conduction when cells are partially decoupled. With reduced coupling,

there is less electrotonic load and reduced axial current flow from a depolarizing cell to down-
stream less depolarized cells. Consequently, there is greater confinement of depolarizing charge
to the depolarizing cell, which depolarizes with a large margin of safety. However, because of the
small axial current, there is a long delay to excitation of the downstream neighboring cell. Thus,

propagation in the fiber proceeds with long conduction delays between cells that depolarize with
high safety margin. This conduction is highly discontinuous, slow (due to the long intercellular
delays), but very robust. Clearly, reduced membrane excitability and reduced cell-to-cell coupling