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Chapter 9
of skeletal muscle myosin. Because the rate of ATP splitting
determines the rate of cross-bridge cycling and, thus, shorten-
ing velocity, smooth muscle shortening is much slower than
that of skeletal muscle. Due to this slow rate of energy usage,
smooth muscle does not undergo fatigue during prolonged
periods of activity. Note the distinction between the two roles
of ATP in smooth muscle: splitting one ATP to transfer a
phosphate onto myosin light chain
(phosphorylation)
starts
a cross-bridge cycling, after which one ATP per cycle is split
(hydrolysis)
to provide the energy for force generation.
To relax a contracted smooth muscle, myosin must be
dephosphorylated because dephosphorylated myosin is unable
to bind to actin. This dephosphorylation is mediated by the
enzyme
myosin light-chain phosphatase,
which is continu-
ously active in smooth muscle during periods of rest and con-
traction (step 6 in Figure 9–34). When cytosolic calcium rises,
the rate of myosin phosphorylation by the activated kinase
exceeds the rate of dephosphorylation by the phosphatase, and
the amount of phosphorylated myosin in the cell increases,
producing a rise in tension. When the cytosolic calcium con-
centration decreases, the rate of phosphorylation falls below
that of dephosphorylation, and the amount of phosphorylated
myosin decreases, producing relaxation.
In some smooth muscles, when stimulation is persistent
and the cytosolic calcium concentration remains elevated, the
rate of ATP splitting by the cross-bridges declines even though
isometric tension is maintained. This condition, known as the
latch state,
occurs when a phosphorylated cross-bridge becomes
dephosphorylated while still attached to actin. In this circum-
stance it can maintain tension in an almost rigorlike state without
movement. Dissociation of these dephosphorylated cross-bridges
from actin by the binding of ATP does occur, but at a much
slower rate than dissociation of phosphorylated bridges. The net
result is the ability to maintain tension for long periods of time
with a very low rate of ATP consumption. A good example of
the usefulness of this mechanism is seen in sphincter muscles of
the gastrointestinal tract, where smooth muscle must maintain
contraction for prolonged periods.
Figure 9–35
compares the
activation of smooth and skeletal muscles.
Sources of Cytosolic Calcium
Two sources of calcium contribute to the rise in cytosolic cal-
cium that initiates smooth muscle contraction: (1) the sarco-
plasmic reticulum and (2) extracellular calcium entering the
cell through plasma-membrane calcium channels. The amount
of calcium each of these two sources contributes differs among
various smooth muscles, some being more dependent on extra-
cellular calcium than the stores in the sarcoplasmic reticulum,
and vice versa.
First we’ll examine the role of the sarcoplasmic reticu-
lum. The total quantity of this organelle in smooth muscle
is smaller than in skeletal muscle, and it is not arranged in
any specifi c pattern in relation to the thick and thin fi la-
ments. Moreover, there are no T-tubules connected to the
plasma membrane in smooth muscle. The small cell diameter
and the slow rate of contraction do not require such a rapid
mechanism for getting an excitatory signal into the muscle
cell. Portions of the sarcoplasmic reticulum are located near
the plasma membrane, however, forming associations similar
to the relationship between T-tubules and the lateral sacs in
skeletal muscle. Action potentials in the plasma membrane
can be coupled to the release of sarcoplasmic reticulum cal-
cium at these sites. In some types of smooth muscles, action
potentials are not necessary for calcium release. Instead,
second messengers released from the plasma membrane, or
generated in the cytosol in response to the binding of extra-
cellular chemical messengers to plasma-membrane receptors,
can trigger the release of calcium from the more centrally
located sarcoplasmic reticulum (review Figure 5–10 for a spe-
cifi c example).
What about extracellular calcium in excitation-contraction
coupling? There are voltage-sensitive calcium channels in the
plasma membranes of smooth muscle cells, as well as calcium
channels controlled by extracellular chemical messengers. The
calcium concentration in the extracellular fl uid is 10,000 times
greater than in the cytosol, thus the opening of calcium chan-
Cross-bridge cycle
produces tension and
shortening
Cross-bridge cycle
produces tension and
shortening
Smooth muscle
Skeletal muscle
Phosphorylated
cross-bridges
bind to actin filaments
Myosin light-chain kinase
uses ATP to phosphorylate
myosin cross-bridges
Ca
2+
–calmodulin complex
binds to myosin
light-chain kinase
Ca
2+
binds to calmodulin
in cytosol
Myosin cross-bridges
bind to actin
Conformational change
in troponin moves
tropomyosin out of
blocking position
Ca
2+
binds to troponin
on thin filaments
Cytosolic Ca
2+
Cytosolic Ca
2+
Figure 9–35
Pathways leading from increased cytosolic calcium to cross-bridge
cycling in smooth and skeletal muscle fi bers.
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