Page 14 - YORAM RUDY BOOK FINAL

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Figure 2.3 Rate dependence of action potential
duration (APD). Model simulations are shown on the
left and corresponding experiments 47-49 on the right. A.
Steady state AP at CL=0.3, 0.5, 1 and 2 sec. B. APD
restitution and adaptation. The black (solid and dashed)
traces show restitution (APD as a function of the
coupling interval of an S2 stimulus following steady-
state pacing at CL ) for various rates of steady-state
s1
pacing (CL for each curve is provided in the figure). The
s1
gray trace is the APD adaptation curve, showing steady-
state APD dependence on pacing rate (S2 coupling
interval = CL in this case). C. Accommodation of APD
S1
following a change of pacing rate from CL=1 sec to
CL=0.5 sec. Adapted from Decker, et. al. [17] courtesy of
The American Physiological Society.
Figure 2.3 shows these rate-
dependent phenomena. 16,17,18,47,48,49
Action potentials at different rates
during steady-state pacing are shown
in Panel A. As rate increases, APD
progressively shortens (adaptation) and
the action-potential notch becomes
more shallow. Panel B shows the adap-
tation curve (gray; APD vs pacing cycle
length) and APD restitution curves
(black; APD vs coupling interval) of
premature action potentials that follow
steady-state pacing at different rates
(cycle length, C , varied from 0.3 sec
Ls1
to 2 sec). As C decreases, restitution
Ls1
curves shift toward shorter APD.
Accommodation is shown in Panel C;
upon acceleration of pacing rate from
cycle length of 1 sec to 0.5 sec (at time
t=0), APD approaches its new (shorter)
steady-state value over a time course of
several minutes. Mechanistically, both
the downward shift of restitution curves
and the process of accommodation
involve increased intracellular sodium
concentration at fast rate, which
augments outward repolarizing I NaK
(stoichiometry 3Na :2K ) to shorten APD.
+
+
I plays an important role in this
Ca,L
2+
process. In response to increased Ca
entry via I at fast rates, forward-mode
Ca,L
I NaCa is augmented, leading to enhanced
+
2+
Ca efflux and Na influx and Na
+
loading of the cell.
The ionic mechanism of rate-
dependent APD adaptation is species
dependent. Figure 2.4 is a comparison
of adaptation in the canine (left panels)
and the guinea pig (right panels). The