Human Physiology, 14th edition (2016)

370 Chapter 12

Role of Ca^2 1 in Muscle Contraction

Scientists long thought that Ca^2 1 only served to form the

calcium phosphate crystals that hardened bone, enamel, and

dentin. In 1883, Sidney Ringer published the results of a sur-

prisingly simple experiment that changed that idea. He isolated

rat hearts and found that they beat well when placed in isotonic

solutions made with the hard water from a London tap. When

he made the isotonic solutions with distilled water, however,

the hearts gradually stopped beating. This could be reversed,

he found, if he added Ca^2 1 to the solutions. This demonstrated

a role for Ca^2 1 in muscle contraction, a role that scientists now

understand in some detail.

In a relaxed muscle, when tropomyosin blocks the attach-

ment of cross bridges to actin, the concentration of Ca^2 1 in

the sarcoplasm (cytoplasm of muscle cells) is very low. When

the muscle cell is stimulated to contract, mechanisms that

will be discussed shortly cause the concentration of Ca^2 1 in

the sarcoplasm to quickly rise. Some of this Ca^2 1 attaches to

troponin, causing a conformational change that moves the tro-

ponin complex and its attached tropomyosin out of the way

so that the cross bridges can attach to actin ( fig. 12.14 ). Once

the attachment sites on the actin are exposed, the cross bridges

can bind to actin, undergo power strokes, and produce muscle

contraction.

to actin is a function of two proteins that are associated with
actin in the thin filaments.
The actin filament—or F-actin —is a polymer formed of
300 to 400 globular subunits ( G-actin ), arranged in a double
row and twisted to form a helix ( fig. 12.13 ). A different type
of protein, known as tropomyosin, lies within the groove
between the double row of G-actin monomers. There are 40 to
60 tropomyosin molecules per thin filament, with each tropo-
myosin spanning a distance of approximately seven actin
subunits.
Attached to the tropomyosin, rather than directly to the
actin, is a third type of protein called troponin. Troponin is
actually a complex of three proteins ( fig. 12.13 ). These are
troponin I (which inhibits the binding of the cross bridges to
actin), troponin T (which binds to tropomyosin), and troponin C
(which binds Ca^2 1 ). Troponin and tropomyosin work together
to regulate the attachment of cross bridges to actin, and thus
serve as a switch for muscle contraction and relaxation. In a
relaxed muscle, the position of the tropomyosin in the thin
filaments is such that it physically blocks the cross bridges
from bonding to specific attachment sites in the actin. Thus,
in order for the myosin cross bridges to attach to actin, the
tropomyosin must be moved. This requires the interaction of
troponin with Ca^2 1.

Figure 12.12 The cross-
bridge cycle. Hydrolysis of ATP and
consequent phosphorylation of the
myosin head is required for activation of
the cross bridge. The release of P i from
the myosin head (dephosphorylation)
causes a conformational change of the
myosin that results in the power stroke.
The binding of a new ATP to the myosin
head allows the cross bridge to release
from the actin.

Cross bridge

binds to actin

Power stroke causes

filaments to slide; ADP

is released

Resting fiber; cross bridge is

not attached to actin

A new ATP binds to

myosin head, allowing

it to release from actin

ATP is hydrolyzed and

phosphate binds to

myosin, causing cross

bridge to return to its

original orientation

Cross bridge

Thick filament

Thin

filament

ADP

Pi

AT P

Myosin head

Pi is released from myosin

head, causing conformational

change in myosin

1

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3

4

5

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