Biomedical Engineering Reference
In-Depth Information
Figure 3
. Model versus experimental action potentials and Ca
2+
transients. Each action potential and Ca
2+
transient is in response to a 1 Hz pulse train, with responses measured in the steady state. (
A
) Experimentally
measured membrane potential (mV, ordinate) as a function of time (msec, abscissa) in normal (solid) and
failing (dotted) canine myocytes. (
B
) Experimentally measured cytosolic Ca
2+
concentration (nmol/L, ordi-
nate) as a function of time (msec, abscissa) for normal (solid) and failing (dotted) canine ventricular myo-
cytes. (
C
) Membrane potential (mV, ordinate) as a function of time (msec, abscissa) simulated using the
normal canine myocyte model (solid), and with the successive downregulation of
I
to1
(dot-dashed, 66%
downregulation),
I
K1
(long-dashed, downregulation by 32%), SERCA2 (rightmost short-dashed, downregula-
tion by 62%) and NCX1 (dotted, upregulation by 75%). (
D
) Cytosolic Ca
2+
concentration (nmol/L, ordinate)
as a function of time (msec, abscissa) simulated using the normal (solid) and heart failure (dotted) model.
(
E
) Normalized peak RyR Ca
2+
release flux (ordinate) as a function of membrane potential (mV, abscissa)
measured experimentally (filled circles) and predicted using the common pool model (solid line). Reprinted
with permission of the Royal Society of London from Winslow et al. (2001) (23).
density of these currents (37). However, downregulation of voltage-gated K
currents is known to occur in HF. Measurements of whole-cell inward rectifier
current
I
K1
show that current density at hyperpolarized membrane potentials is
reduced in HF by ~50% in human (38) and by ~40% in dog (36). Measurements
