Page 101 - YORAM RUDY BOOK FINAL

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Figure 3.19. Rate-dependent discontinuous transmural conduction with F2004L mutant I .
Na
A. Propagating AP is shown at selected cells of the fiber during pacing at CL=300 msec (left)
and 1000 msec (right) for WT (top), F2004L (middle), and F2004L with 50% I (50% G , bottom).
T0
t0
APs are normal and propagation is uniform for WT during both slow and fast pacing. Conduction
velocity is 45.3 and 44.4 cm/sec, respectively. For mutant F2004L, conduction is slowed to
25.2 cm/sec at CL=300msec, but remains uniform. However, at CL=1000 msec there is a long
delay of 116.5 msec before excitation of cell 150 (black traces show AP at every fifth cell between
cells 115 and 150). When G is reduced to 50%, the delay is eliminated. B. Surface plot showing
T0
APs in space and time for the F2004L mutant fiber. The excitation wave is decremental and
encounters a long delay beyond the mid-myocardial (M) to epicardial (epi) transition region.
The delayed APs have very slow upstrokes. Note that the dome of the M-cell AP is of higher
magnitude than the peak of its upstroke; it therefore generates greater driving force for
downstream axial current (I axial ). C. Conduction velocity does not depend on pacing rate for WT,
but slowing by the F2004L mutation is rate dependent (much greater at slow rate). With 50% G ,
T0
slowing is relatively rate independent. D. I axial for cells along the mutant fiber at CL=1000 msec.
Both peak inward (negative) and outward (positive) I axial decrease with cell number along the fiber,
indicating that there is progressive decrease in depolarizing current as propagation proceeds.
Cell 150 (red) is excited after a long delay. The initial I axial influx is too small to excite this cell, but a
later influx supported by the dome of excited upstream cells is sufficient to cause excitation. This
dome-driven current appears as late outward (positive) deflection in I axial for epi cells 120 (blue) and
135 (green). From Bébarová et. al. [227] courtesy of The American Physiological Society.