44
CARDIOVASCULAR PHYSIOLOGY CONCEPTS
Sarcolemma
Ca++
■ FIGURE 3.3 Role of calcium (Ca++) in cardiac excitation-contraction coupling. During action potentials,
Ca++ enters cell through L-type Ca++ channels. This so-called trigger Ca++ is sensed by the “feet” of the
calcium-release channel (ryanodine receptor,
RyR)
of the sarcoplasmic reticulum
(SR),
which releases
Ca++ into the cytoplasm. This Ca++ binds to troponin-C
(TN-C),
inducing a conform ational change in the
troponin-tropom yosin complex so that movement of the troponin-tropom yosin complex exposes a
m yosin-binding site on actin, leading to ATP hydrolysis and movement of actin relative to myosin. Ca++ is
resequestered into the SR by an ATP-dependent Ca++ pump, sarcoendoplasmic reticulum calcium ATPase
(SERCA)
that is inhibited by phospholamban. Not shown are Ca++ pumps that remove Ca++ from the cell.
sarcoplasmic reticulum that are adjacent to
the T tubules. Between the terminal cisternae
and the T tubules are electron-dense regions
called feet that are believed to sense calcium
between the T tubules and the terminal cister-
nae. Closely associated with the sarcoplasmic
reticulum are large numbers of mitochondria,
which provide the energy necessary for myo-
cyte contraction.
CALCIUM CYCLING AND THE FUNCTION
OF REGULATORY PROTEINS
When an action potential causes depolariza-
tion of a myocyte (see Chapter 2), it initi-
ates excitation-contraction coupling. When
the myocyte is depolarized,
calcium ions
enter the cell during the action potential
through long-lasting (L-type) calcium chan-
nels located on the external sarcolemma and
T tubules (see Fig. 3.3). It is important to
note that a relatively small amount of calcium
enters the cell during depolarization. By itself,
this calcium influx does not significantly
increase intracellular calcium concentrations
except in local regions just inside the sarco-
lemma. This calcium is sensed by the “feet”
of the calcium-release channels (ryanodine
receptors, or ryanodine-sensitive calcium-
release channels) associated with the termi-
nal cisternae. This triggers the subsequent
release of large quantities of calcium stored in
the terminal cisternae through the calcium-
release channels, which increases intracel-
lular calcium concentrations 100-fold, from
about 10-7 to 10-5 M. Therefore, the calcium
that enters the cell during depolarization is
sometimes referred to as “trigger calcium.”
The
free
calcium binds to TN-C in
a
concentration-dependent manner. This induces
a conformational change in the regulatory
complex such that the troponin-tropomyosin
complex moves away from and exposes a
myosin-binding site on the actin molecule.
The binding of the myosin head to the actin
results in ATP hydrolysis, which supplies
energy so that a conformational change can
occur in the actin-myosin complex.
This
results in a movement (“ratcheting”) between
the myosin heads and the actin. The actin
and myosin filaments slide past each other,
thereby shortening the sarcomere length (this
is referred to as the sliding filament theory
of muscle contraction) (Fig. 3.4). Ratcheting
cycles will occur as long as the cytosolic
calcium remains elevated. Toward the end of
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