Muscle
285
oped by smooth muscles is similar to that developed by skel-
etal muscle.
The isometric tension produced by smooth muscle
fi bers varies with fi ber length in a manner qualitatively similar
to that observed in skeletal muscle—tension development is
highest at intermediate lengths and lower at shorter or longer
lengths. However, in smooth muscle signifi cant force is gener-
ated over a relatively broad range of muscle lengths compared
to that of skeletal muscle. This property is highly adaptive
because most smooth muscles surround hollow structures and
organs that undergo changes in volume with accompanying
changes in the lengths of the smooth muscle fi bers in their
walls. Even with relatively large increases in volume, as during
the accumulation of large amounts of urine in the bladder, the
smooth muscle fi bers in the wall retain some ability to develop
tension, whereas such distortion might stretch skeletal muscle
fi bers beyond the point of thick- and thin-fi lament overlap.
Smooth Muscle Contraction
and Its Control
Changes in cytosolic calcium concentration control the
contractile activity in smooth muscle fi bers, as in striated
muscle. However, there are signifi cant differences in the way
calcium activates cross-bridge cycling and in the mecha-
nisms by which stimulation leads to alterations in calcium
concentration.
Cross-Bridge Activation
Because smooth muscle lacks the calcium-binding protein
troponin, tropomyosin is never held in a position that blocks
cross-bridge access to actin. Thus, the thin fi
lament cannot
act as the switch that regulates cross-bridge cycling.
Instead,
cross-bridge cycling in smooth muscle is controlled by a calcium-
regulated enzyme that phosphorylates myosin.
Only the phos-
phorylated form of smooth muscle myosin can bind to actin
and undergo cross-bridge cycling.
The following sequence of events occurs after a rise in
cytosolic calcium in a smooth muscle fi ber (
Figure 9–34
):
(1) Calcium binds to calmodulin, a calcium-binding protein
that is present in the cytosol of most cells (Chapter 5) and
whose structure is related to that of troponin. (2) The cal-
cium-calmodulin complex binds to another cytosolic protein,
myosin light-chain kinase,
thereby activating the enzyme.
(3) Active myosin light-chain kinase then uses ATP to phos-
phorylate myosin light chains in the globular head of myosin.
(4) Phosphorylation of myosin drives the cross-bridge away
from the thick fi lament backbone, allowing it to bind to actin.
(5) Cross-bridges go through repeated cycles of force genera-
tion as long as myosin light chains are phosphorylated. A key
difference here is that calcium-mediated changes in the thick
laments turn on cross-bridge activity in smooth muscle,
whereas in striated muscle, calcium mediates changes in the
thin fi
laments.
The smooth muscle form of myosin has a very low rate of
ATPase activity, on the order of 10 to 100 times less than that
Inactive myosin
light-chain kinase
Active calcium-
calmodulin myosin
light-chain kinase
Myosin light-
chain phosphatase
(Ca
2+
)
Inactive
calmodulin
Active Ca
2+
calmodulin
Cytosolic Ca
2
+
ATP
AD
P
2
3
4
5
6
1
Unphosphorylated myosin,
cross-bridge held near
thick filament
Phosphorylation
forces cross-bridge
toward thin filamen
t
PO
4
Cross-bridge
cyclin
g
Smooth muscle cell cytosol
Figure 9–34
Activation of smooth muscle contraction by calcium. See text for description of the numbered steps.
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