Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 15 Skeletal Muscle Function
AM ADP P
AM • ADP • P
D . Muscular Energetics
A
A
Force Generation
Step
M
M
AM
+
ATP
AM* • ADP • P
AM • ATP
M
A
M
M • ATP P
M* • ADP • P A
Muscular contraction results from the transformation of
chemical energy into mechanical energy. The energy for
contraction is derived from the hydrolysis of adenosine triphosphate
(ATP) into adenosine diphosphate (ADP) and
inorganic phosphate ( Fig. 15-2 ) catalyzed by myosin adenosine
triphosphatase (ATPase) activity in the myosin head.
Chemically, the transformation of energy is associated with
the cyclical association and disassociation of the contractile
proteins actin and myosin, whereas mechanically the
transformation is associated with shortening of sarcomeres,
which is achieved by conformational changes of the myosin
molecules that result in sliding of the overlapping arrays
of thick and thin myofilaments ( Fig. 15-4 ) ( Eisenberg et al. ,
1972 ; Huxley et al. , 1983 ; Lymn and Taylor, 1971 ).
In the noncontracting state, actin and myosin are combined
at the cross-bridges (step 1, Fig. 15-4 ), and the angle of
attachment between the cross-bridge heads and the actin filaments
is 45 degrees. Binding of ATP to each globular head
(two molecules ATP/myosin molecule) results in a rapid
disassociation of actin and myosin (step 2, Fig. 15-4 ). ATP
hydrolysis is rapid when myosin is not associated with actin
resulting in the release of phosphate and ADP. The globular
head of myosin moves to a new location on the thin filament
(step 3, Fig. 15-4 ), which permits the angle of attachment to
become 90 degrees when the globular head recombines with
the actin filament (step 4, Fig. 15-4 ). This recombination
step between the globular head and actin is controlled by the
regulatory proteins troponin and tropomyosin in response
to calcium ion concentrations. The force for contraction is
generated by movement of the cross-bridge head to a 45
degree angle of attachment (step 5, Fig. 15-4 ), and the cycle
is completed with the detachment of the hydrolytic products
of ATP from the head (step 6, Fig. 15-4 ). With the formation
of ATP through rephosphorylation (step 7, Fig. 15-4 ), the
A
M
Myosin
Cross-Bridge
Cycle
A
M
A
A
M
Ca 2
Troponin-Tropomyosin
FIGURE 15-4 Muscular contraction results from the cyclical association
and disassociation of actin (A) and myosin (M) in which conformational
changes occur in the cross-bridge linkages between the thick and
thin myofilaments, associated with the hydrolysis of ATP.
cycle may be repeated. Measurements indicate that each
cycle (stroke) shortens a sarcomere by 12 nm ( Barden and
Mason, 1978 ).
Rigor mortis, the rigid and stiff condition of skeletal
muscles that develops following death, involves cessation
of the cross-bridge cycle in the post-force-generating step
(step 6, Fig. 15-4 ). After death, when all ATP stores have
been utilized, disassociation of actin and myosin will not
occur, and the contraction cycle is terminated with a large
number of actin myosin complexes formed with the myosin
heads set at 45 degrees.
III . HETEROGENEITY OF SKELETAL
MUSCLE
A . Gross Muscle Coloration
The first indication that different muscles had different
physiological prosperities arose from the observation that
there was variation in muscle coloration not only among
species of animals, but also among individual muscles
within the same individual. As a result of these differences
in coloration, the terms “red ” and “white ” were introduced
to distinguish between muscles of different gross coloration.
Red coloration of muscles was subsequently found to
be due to the presence of myoglobin and other cytochromes
within the myofibers. Numerous biochemical, histochemical,
and physiological studies have since been conducted
to detail a variety of differences in both the metabolic and
contractile properties of “red ” and “white ” skeletal muscle.
B . Physiological Properties
The speed of contraction of red muscles was most often
found to be slower than that of white muscles in a variety
of animals. In addition, redness of a muscle was associated
with the development of tetanus at lower frequencies
of stimulation, the development of smaller twitch tensions,
and a greater resistance to fatigue. Conversely, white
muscles required greater frequencies of stimulation for the
development of tetanus, developed larger twitch tensions,
and tended to fatigue quickly. From this data, the terminology
of slow-contracting or slow-twitch and fast-contracting
or fast-twitch muscles evolved. Moreover, because speed of
contraction was closely associated with gross muscle coloration,
the terms “ red ” and “ white ” came to be used interchangeably
with “ slow ” and “ fast, ” respectively. However,
there are numerous exceptions to this association of gross
coloration with physiological properties of contraction.
Therefore, direct associations must not be assumed.
C . Motor Units
The morphological and functional unit of skeletal muscles
is the motor unit ( Fig. 15-5 ). The motor unit is composed