Page 77 - Cardiac Electrophysiology | A Modeling and Imaging Approach
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        Figure 3.3. Effect of decreasing gap junction conductance on AP upstroke velocity, dV /dt          max
                                                                                                       m
        (solid line) and peak I  (short-dashed line). dV /dt   max  for a continuous fiber (long-dashed line) is
                                                           m
                               Na
        also shown for comparison (in this case, the “gap junction conductance” is spread evenly along
        the continuous fiber that does not contain discrete cells). I   Na,max  decreases slowly initially and then
        abruptly toward conduction block (indicated by the black horizontal bar) at high level of inter-
        cellular uncoupling. The sharp decline is due to dynamic inactivation of Na  channels during slow
                                                                                          +
        depolarization by a small axial current through low conductance gap junctions. Discontinuous
        dV /dt max  increases initially due to greater local confinement of depolarizing charge; it then
           m
        decreases following the decline of I   Na,max . In contrast, continuous dV /dt max  is constant, unaffected
                                                                                  m
        by changes in fiber conductance. Adapted from Shaw and Rudy [174], with permission from
        Wolters Kluwer Health, Inc.



        locations were simulated in a 1-dimensional multi-cellular fiber model, where each cell was

        divided into 20 excitable elements . Similar spatial behavior was observed in a detailed
                                              180
        2-dimensional model of canine myocardium . The model represented realistic cell shapes and
                                                         181
        sizes. It accounted for the spatial distribution of gap junctions, with different values of conductance
        for those at cell ends or lateral cell borders (each cell was composed of up to 36 excitable elements).

        Simulated propagation in this model clearly demonstrated and determined the cellular-scale
        mechanism of direction-dependent conduction (“anisotropic conduction”) in cardiac tissue.            182-185
        Similar in principle to 1-dimensional conduction at various degrees of gap junction coupling,
        the slower velocity and higher dV /dt    max  values that are measured for transverse compared to
                                             m
        longitudinal propagation (relative to the long axis of the cell) are explained in terms of source-sink
        relationships.
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