physiology of muscle fatigue

1. Muscle : Fatigue
contraction and relaxation
Ali Faris
References : Guyton book & Netter`s physiology &
Medical physiology

2. •Muscle Fatigue : Prolonged and strong
contraction of a muscle leads to the well-known
state of muscle fatigue.
•Studies in athletes ‫رياضيون‬ have shown that
muscle fatigue increases in almost direct
proportion to the rate of depletion ‫نقصان‬ of
muscle glycogen.

3. • fatigue results mainly :
1. from inability of the contractile and metabolic processes of the muscle
fibers to continue supplying the same work output.
2. experiments have also shown that transmission of the nerve signal
through the neuromuscular Junction can diminish at least a small
amount after intense prolonged muscle activity, thus further
diminishing muscle contraction.
3. Interruption of blood flow through a contracting muscle leads to
almost complete muscle fatigue within 1 or 2 minutes because of the
loss of nutrient supply, especially the loss of oxygen.

4. When and how the muscle fatigue happen?
• During a period of heavy exercise,
• especially when working above 70% of maximal aerobic capacity,
• skeletal muscle is subject to fatigue.
• The speed and force of contraction are diminished, relaxation time is
prolonged,
• and a period of rest is required to restore normal function.

7. Contraction and relaxation of
muscle

8. Excitation-Contraction
Coupling

9. Excitation-Contraction Coupling
1. The axonal action potential in the motor neuron results in acetylcholine
release at the neuromuscular junction.
2. Acetylcholine is bound on the postsynaptic membrane (sarcolemma),
resulting in opening of a cation channel and infl ux of Na.
3. An action potential is produced and spreads into the transverse
tubule, resulting in release of Ca2 from the sarcoplasmic
reticulum.
4. Cross-bridge formation is initiated, and muscle contraction is
produced.
5. Ca2 is resequestered into the sarcoplasmic reticulum by
Ca2-ATPase, terminating contraction.

10. 1. Sarcomere
2. Z band
3. I band
4. A band
5. H zone

11. Comment: During contraction of skeletal muscle, the thick myosin
fi laments that extend through the A band cyclically form cross bridges
with the thin actin fi laments, resulting in sliding of the interdigitated
myosin and actin fi laments and shortening of sarcomeres.
As a result, Z bands move closer together, and I bands and H zones
narrow.

12. Biochemical Mechanics of
Muscle Contraction

13. Biochemical Mechanics of Muscle Contraction
1. In resting muscle, adenosine triphosphate (ATP) is bound to myosin
head groups and is partially hydrolyzed, producing a highaffi
nity binding site for actin. However, tropomyosin blocks the
binding site for the myosin head group on actin, and the muscle
remains relaxed.
2. Ca2 is released from the sarcoplasmic reticulum in response to
an action potential and binds to troponin. Tropomyosin is displaced
from the myosin binding site of actin, allowing cross-bridge
formation between the myosin head group and actin.

14. 3. Adenosine diphosphate (ADP) and (Pi) are released from the
myosin head group, and the head group fl exes, producing sliding
of the fi laments and shortening of the sarcomere.
4. ATP binds to the myosin head group, releasing it from the
actin. Partial hydrolysis of the ATP results in recocking of the
head group and produces a high-affi nity actin binding site. As
long as Ca2 remains elevated, the cross-bridge will reform, and
the cycle will continue (1), producing further shortening;
otherwise, the muscle will relax.

15. Excitation-Contraction Coupling of Smooth
Muscle

16. 1. Ca2
2. Phospholipase C
3. Inositol trisphosphate (IP3)
4. Calmodulin
5. Ca-calmodulin
6. Myosin kinase
7. Myosin phosphatase

17. 8. Intracellular free Ca2 (1) can be elevated by depolarization of the
cell membrane and opening of Ca2 channels. It can also be elevated
by binding of a ligand to a membrane receptor. In the latter
case, this activates phospholipase C (2), which cleaves phosphatidyl
inositol to produce IP3 (3); IP3 binds to the sarcoplasmic reticulum
causing release of stored Ca2. In either case, Ca2 binds to
the calcium binding protein calmodulin (4), forming Ca-calmodulin
(5). The Ca-calmodulin activates myosin kinase (6), initiating crossbridge
formation and the contraction cycle, which continues as
long as Ca2 is elevated. Otherwise, dephosphorylation of myosin
by myosin phosphatase (7) ends the cycle. The latch state occurs
when myosin is dephosphorylated while bound to actin, resulting
in sustained contraction without requirement for additional ATP
hydrolysis.

18. Cardiac Muscle Structure
1. T tubule
2. Sarcomere
3. Sarcoplasmic reticulum
4. Intercalated disk
5. Thin fi lament (mainly actin)
6. Thick fi lament (myosin)

22. Relaxation of muscle
Steps in relaxation:
1- After a fraction of a second, the calcium ions are pumped actively back into the
sarcoplasmic reticulum by a Calcium membrane pump (active transport, needs ATP i.e.
both contraction and relaxation need energy)they are going to diffuse into the terminal
cisterns to be released by the next action potential.
2- The release of calcium ions from Troponin C,
3- Then cessation of binding between actin and myosin (i.e. tropomyosin returns to its
site) this removal of calcium ions causes the muscle contraction to stop.
If Ca ions stay in high concentration outside the SR, or if the Ca ions transport to the
SR is inhibited, there will be persistent contraction and no relaxation even though there
are no more action potentials and this will result in what is called contracture (sustained
contraction).