Page 13 - YORAM RUDY BOOK FINAL

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Figure 2.2 Major ionic currents during the
action potential (AP). Shown are the AP
(repeated at top of both columns for
reference), the calcium transient (free Ca 2+
in the myoplasm during the AP, [Ca ] ), and
2+
i
selected ionic currents that determine the AP
morphology (current symbols are defined in
Figure 2.1; V , membrane potential). A canine
m
epicardial cell model (HRd model 16,17 ) paced at
a steady-state cycle length CL=1000msec, was
used in the simulation. Source: Rudy [43a].
Reproduced with permission from Elsevier.
it changes direction to operate in its “direct
mode” of calcium extrusion, generating an
inward current that slows repolarization and
prolongs the action potential duration (note that
I NaCa = I NaCa,ss + I NaCa,i is shown in Figure 2.2). I the
K1,
inward rectifier potassium current, increases
to a large peak late in the repolarization phase,
accelerating final V repolarization to its resting
m
value and stabilizing the membrane at its
resting state.
2.4 Rate Dependence of the Action Potential
Shortening of action potential duration
(APD) as heart rate increases is essential for
normal cardiac function. With APD
shortening, ventricular relaxation during the
diastolic interval (DI) is maintained at fast rate,
allowing sufficient time for ventricular filling
and adequate cardiac output. This process is
known as rate-dependent APD adaptation
(or simply adaptation) and concerns APD during
steady-state pacing at different rates. Another
rate-dependent phenomenon is APD restitution
of premature action potentials. When the cell is
excited prematurely at a short coupling interval
from a previous action potential, various ion
channels and ion cycling processes (in particular
calcium cycling) do not have sufficient time to
return to their steady-state conditions.
Consequently, the premature action potential
is generated from a different set of initial
conditions that depend on the coupling interval
from the previous beat. A third rate-dependent
phenomenon is APD accommodation, a
dynamic process that determines the time
course to a new steady-state following change
of pacing rate.