oped by smooth muscles is similar to that developed by skel-
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
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
act as the switch that regulates cross-bridge cycling.
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 (
(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
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
cross-bridge held near
toward thin filamen
Smooth muscle cell cytosol
Activation of smooth muscle contraction by calcium. See text for description of the numbered steps.