Biomedical Engineering Reference
In-Depth Information
Figure 4
. (
A
) Structure of the LCC-RyR complex, denoted as the functional unit (FU). A single LCC
in the sarcolemmal membrane is associated with 5 RyR in the closely apposed JSR membrane. ClCh
denotes a single Ca
2+
-modulated Cl
-
channel that is thought to be co-located in the dyadic space. (
B
)
Structure of the Ca
2+
release unit (CaRU). Each CaRU consists of 4 FUs, with Ca
2+
diffusion between
adjacent FUs and into the surrounding cytosolic space. (
C
) Solid line is an action potential (mem-
brane potential in mV, left ordinate; time in msec, abscissa) predicted by the local-control myocyte
model. Dotted line is the fraction of channels (right ordinate) not voltage inactivated, and the dashed
line is the fraction not Ca
2+
-inactivated during the action potential shown by the solid line. (
D
) Behav-
ior of the common pool myocyte model when the balance between voltage- and Ca
2+
-inactivation is
as shown in panel
C
. Note the instability of action potentials. (
E
) Peak Ca
2+
flux (ordinate) through
RyRs (open symbols) and LCCs (filled symbols) as a function of membrane potential (mV, abscissa).
(
F
) EC coupling gain (ordinate, ratio of peak RyR to LCC flux) as a function of membrane potential
(mV, abscissa).
small cluster
of RyRs located in the closely apposed (~12 nm) JSR membrane.
Thus, the local control hypothesis asserts that release is all-or-none at the level
of these individual groupings of LCCs and RyRs (referred to as the functional
unit). However, LCC:RyR clusters are physically separated at the ends of the
sarcomeres (57). These clusters therefore function in an approximately inde-
pendent fashion. The local control hypothesis asserts that graded control of SR
