Biochemistry Lecture Outline: Muscle Contraction

All Muscle Tissues share these general properties:

1) Contractility – muscle cells shorten when electrically stimulated, generating force.

2) Excitability – muscle and nervous tissue respond to electrical stimulation = excitable tissue.

3) Extensibility – muscle tissue can stretch when a force is applied to it.

4) Elasticity – muscle tissue can recoil to its original shape when the force stretching it is removed.

There are 3 types of Muscle Tissue:

1) Skeletal Muscle – attached to skeletal system (bones).

2) Cardiac Muscle – found in the heart.

3) Smooth Muscle – in walls of internal organs (e.g. stomach, small intestine) and in blood vessels.

Table 1. Fill in this table with the comparison of the three types of muscle tissue.
Qualities Skeletal Muscle Cardiac Muscle Smooth Muscle
Cell shape, structure

Location in body

Banding pattern?

Control

Strength

Fatigue

Functions of the Skeletal Muscular System

1. Body Movement

2. Protection of deeper tissues

3. Guards entrances and exits

4. Generates body heat

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Muscle Vocabulary

There are certain terms that are used when discussing muscle tissue, like a vocabulary list. Here is a brief
summery of some common terms that are specialized for muscle.

Often a single muscle cell is called a muscle fiber (especially for skeletal muscle). The sarcoplasm is the
cytoplasm of muscle cells. The sarcolemma is the plasma membrane of the muscle cell (fiber). The
sarcoplasmic reticulum (SR) is a specialized type endoplasmic reticulum (ER) in muscle cells for storing
intracellular Ca2+ ions. The release of these Ca2+ ions is crucial for the contraction of muscle cells.

The lateral portions of the SR can be called the “lateral sacs” or the “terminal cisternae”, they are located
close to the transverse tubules (t-tubules). The t-tubules are invaginations of the sarcolemma and they act
to quickly spread the action potential of the muscle across the entire cell.

Two Contractile Proteins

A myofibril is a bundle of contractile and elastic proteins responsible for muscle contraction, containing
the two major contractile proteins, thick filament (myosin) and the thin filament (actin). Actin also has
two regulatory proteins associated with it.

Actin – is a thin contractile protein that is attached to the Z discs of the sarcomere. There are active sites
on actin and when these are exposed, myosin heads will bind with the active sites of actin. Actin also has
two regulatory proteins, troponin and tropomyosin, that are closely associated with it (see below).

Myosin – is a thick contractile protein with many myosin heads radiating off the thick body of myosin.
Each myosin head has two binding sites on it, one for actin (the other contractile protein) and one to bind
and hydrolyze ATP. Myosin has a high affinity for actin and the bond between actin and myosin is called
a crossbridge.

Two Regulatory Proteins

As we have already seen, the sarcomere is made mostly of actin and myosin, these two are considered the
contractile proteins. There are also two regulatory proteins in the sarcomere that are associated with the
contractile protein actin. They are troponin and tropomyosin.

Troponin – binds Ca2+ when the levels of Ca2+ inside the sarcoplasm increase.

Tropomyosin – covers the active site on actin. When tropomyosin is in place, actin and myosin are
prevented from binding.

The Sarcomere
The sarcomere is the functional unit of skeletal muscle. A functional unit is the smallest part of the
‘whole’ that does the job of the entire structure. A sarcomere is the smallest element in skeletal (and
cardiac) muscle that contracts and generates force when electrically stimulated. The sarcomere is arranged
such that the thick and thin filaments ‘slide’ past each other during contraction, thus, the theory that
explains muscle contraction is called “The Sliding Filament Theory”. None of the contractile proteins
(actin or myosin) shorten or lengthen during contraction, they move past one another during contraction
but do not change their length.
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The striations of skeletal and cardiac are created by the banding pattern that exists within the sarcomere.
These bands include the A band, I band and H band (or zone). Other structures of the sarcomere include
the central M line and two Z disks, one at each end of the sarcomere.

If we outline what each band is comprised of and then consider how these bands change during
contraction, this will give us insight into how the sarcomere shortens to generate tension.

The H band - contains myosin (the thick filament) only, with no overlap of actin in this band.

The I band - contains actin (the thin filament) only, with no overlap of myosin in this band.

The A band - contains all of the myosin, regardless of how much actin is overlapping.

The width of some bands change during contraction, the discovery of this was what led to the notion of
the sliding filament theory. In class we will analyze the structure of the sarcomere and as we discuss the
way the bands are arranged, it will hopefully be clear which bands change and which do not.

The H and I bands shorten during contraction and they also lengthen when the sarcomere is stretched. The
A band does not shorten during contraction or lengthen when stretched. The A band is all of the myosin,
so it cannot change its length. Because myosin is very thick compared to actin, the A band (which is all of
the myosin) is sometimes called the Dark Band. Also, the I band (made from actin only) is sometimes
called the Light Band.

Summary of Biochemical Events of Muscle Contraction

1. Nerve impulse arrives at neuromuscular junction (neuron to muscle cell communication).

2. Acetylcholine (ACh) is released from motor neuron and diffuses across to the motor end plate.

3. ACh binds with nicotinic receptors at the motor end plate (a specialized portion of sarcolemma).
Receptors are linked to ligand gated ion channels, allowing Na+ influx (plus a little bit of K+ efflux),
resulting in the depolarization of the muscle cell membrane. This results in a motor end plate
potential, which becomes an action potential (AP) in muscle cells.

4. The impulse (AP) is spread very quickly through out the cell by the transverse ("T") tubules. Located
on the T-tubules are the dihydropyridine (DHP) receptors that are mechanically linked to the lateral
sacs (terminal cisternae) of the sarcoplasmic reticulum (SR). When triggered by the change in
membrane potential (AP) traveling down the t-tubules, the DHP receptors mechanically opens gates
on the SR. This then causes the SR to release the Ca2+ it has stored there into the cytosol
(sarcoplasm) of the skeletal muscle.

5. The increase in [Ca2+]i binds to the regulatory protein troponin, causing it to change shape and move.

6. The movement of troponin then moves tropomyosin away from covering the active site on actin, thus
exposing the myosin binding site on actin.
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7. Due to the strong affinity between them, the myosin head binds to the actin (crossbridge).

8. Crossbridge formation stimulates ATPase activity, and allows the power stroke to occur. The power
stroke is the 'pulling' of actin toward the M line by the pivoting of the myosin head. The myosin head
is going from a high E state to a low E state during the power stroke (PE converted to KE).

9. If more ATP is available, then the crossbridge is broken and myosin releases actin. This allows
for the repositioning of the myosin head into the high energy state.

10. Then, if the nerve impulse is still present, steps 7 through 9 will be repeated.

This muscle contraction will continue until: 1) the impulse stops or 2) fatigue occurs.

If Nerve Impulse Stops:

1. Ca2+ will be pumped back into SR (re-sequestered) by active transport (Ca2+ATPase).

2. Without the increased [Ca2+]i, troponin is no longer bound to Ca2+ and the tropomyosin then moves
back over to cover the binding sites on actin. Thus crossbridges formation cannot occur.

3. When all the myosin heads detach, actin slides back to its original position and the muscle relaxes.

Metabolism of Muscle Tissue: Energy Transfer

The direct energy source for muscle work is ATP. The immediate source of E required for muscle
contraction is ATP and contraction can continue for a long time as long as there is adequate ATP. The
supply of ATP depends on 1) O2 availability and 2) organic E sources (e.g., glucose, glycogen, lipids).

During the course of exercise (or physical activity), different mechanisms of ATP synthesis are used
depending on the intensity and duration of exercise. There are three main sources of ATP generation:

 Immediate  Short Term  Long Term

Creatine-Phosphate Glycolysis Oxidative Phosphorylation

 Immediate - The Creatine-Phosphate or Phosphogen System

Creatine-P ADP
Creatine
Kinase
Creatine ATP
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The enzyme creatine kinase takes a high E phosphate from creatine phosphate and adds it to ADP to very
quickly make ATP available for the cell. This 'immediate' ATP source is used when running the 100 m
dash (from 6 to 10 sec) or the first 1 min of a brisk walk. This supplies the active muscle with ATP
anaerobically (without O2), as the cardio-respiratory system cannot yet deliver O2 fast enough to meet the
huge demands of the muscle tissue. It very quickly supplies ATP but its supply is limited.

 Short Term - Glycolysis

As the Phosphogen system is exhausted (as Creatine-P in the cell runs out), the muscle tissue must
continue to 'buy time' until the cardio-respiratory system can supply enough O2 to meet ATP generation
aerobically. The cell mobilizes its glycogen stores for the generation of ATP by glycolysis - again an
anaerobic mechanism. This system can also be called the Glycogen-Lactic Acid System. It can produce
ATP for about 30 to 40 seconds of maximal muscular activity, e.g., a run around the bases from an infield
homerun. Glycolysis is fairly fast, but is inefficient, (1 glucose generates only 2 ATP). Another draw back
is that glycolysis generates lactic acid. When lactic acid builds up, it lowers the surrounding pH and the
proteins in muscle begin to denature, resulting in muscle fatigue.

 Long Term - Oxidative Phosphorylation

After about 40 seconds of maximal activity, the cardio-respiratory system finally catches up to supply
enough O2 to meet ATP generation aerobically. This last method (oxidative phosphorylation) requires
oxygen and takes longer to generates ATP but is much more efficient (1 glucose generates 38 ATP). If
exercising for more than 10 minutes, over 90% of ATP is produced aerobically. When vigorously
exercising, the consumption rate of O2 may increase 3 to 4 times the levels at rest in order to keep ATP
production up with demand. Individuals breath heavily at first, then the pattern of breathing stabilizes at a
higher level. Fatigue (for various reasons) is a factor in how long an individual can continue the activity.

Muscle Fatigue
Muscle fatigue is a progressive weakness and loss of muscle contraction from prolonged use of muscle.
Listed below are some of the causes of muscle fatigue.

1. The organic sources (e.g., glucose or glycogen) are consumed decrease in ATP available.

2. ATP shortage slows Na+/K+ pumps; RMP altered and decrease excitability of cell.

3. K+ rushing out of cell each AP also decrease excitability of cell (decreased [K+]i).

4. Lactic acid build up decrease in pH impairs contractile mechanisms.

5. Motor nerve fibers exhaust ACh at synapse, cannot stimulate muscle. Called "junctional fatigue".

6. CNS (origin of signals) also experiences fatigue, for example "mental fatigue".

Other Types of Contractions

Cramps: action potentials fire at abnormally high rate (higher than when at maximum voluntary
contraction) causing sustained tetanus contraction. Thought to be to electrolyte imbalance.
Convulsions: violent, involuntary contractions of groups of muscles.
Fibrillation: rapid, irregular, uncoordinated muscle contractions (i.e. ventricular fibrillation in the heart).
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Muscle Twitch: Rapid muscle contraction in response to a single stimulus Periods or Phases of a twitch:
1. Latent
2. Contraction
3. Relaxation

Graded Contractions
How do we get Graded (varied) Contractions? Since muscle cells obey the "all or none" law, we must
have some way of getting graded responses.

1. Temporal Summation: An increase in the frequency of stimulatory nerve impulses giving a stronger
contraction. Incomplete tetanus: some partial relaxation between contractions. Complete tetanus: no
relaxation between next contraction (thus a maximum sustained contraction is achieved).

2. Spatial Summation: Contracting a varying numbers of muscle cells by varying the number of motor
units involved. Motor unit: One motor neuron and all the muscle fibers it stimulates (innervates).

Examples of different motor unit sizes:

Laryngeal muscle: 2 cells/motor unit.
Rectus muscle (eye): about 10 cells/motor unit
Tensor tympani (ear): 10-125 cells/motor unit.
Gastrocnemius: about 2,000 cells/motor unit. (Quadriceps: about 3,000 cells/motor unit).

3. Length of Sarcomere: A stretched muscle will contract with a stronger force than an unstretched one.
Why? The length of the sarcomere has an impact on force generation. There is an optimal length at which
the muscle generates the most force during contraction. If the sarcomere is too short or too long, it will
generate less force compared to the optimal length of the sarcomere.

Muscle Growth and Differentiation

There is no mitosis of skeletal muscle tissue in adult, in other words, it does not multiply in number in
order to get larger. Muscle enlargement results from hypertrophy of cells - hypertrophy of a cell is when
the cell gets larger in size, typically by being used more. Atrophy is when the cell gets smaller in size,
typically from a reduction in use.

During Hypertrophy there is an increase 1 through 7. During Atrophy there is a decrease in 1 through 7.
1. Myofibrils (actin & myosin) in muscle cell.
2. Mitochondria.
3. Enzymes.
4. Stored organic materials (i.e., fat & glycogen).
5. Creatine-phosphate.
6. ATP
7. Efficiency of the muscle.
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Properties of Slow (Red) and Fast (White) Twitch Skeletal Muscle Fibers
Slow Twitch (Red Fibers) Fast Twitch (White Fibers)
Tonically active much of the time. Relaxed most of the time.
Under-go very little hypertrophy. Under-go hypertrophy.
Important in endurance (jogging). Important in brute strength (kicking).

At birth all muscle fibers are red (changes later with activity). Most muscles contain about 50% of each.
Some contain all red (posture). None contain more than 50% white. All the muscle fibers in one motor
unit are the same (i.e., all red or all white). The table below compares the properties of slow and fast
twitch muscle fibers.

Properties Slow (Red) Fast (White)

Contraction time (onset) 75 msec (slow onset) 25 msec (fast onset)

Contraction duration longer shorter
Diameter of muscle fiber Small Large
Myosin ATPase activity Low High
Glycogen storage Low High
1o ATP source (Metabolism) Oxidative Phosphorylation Glycolysis
Mitochondrial content High Low
Myoglobin content High Low
Blood supply High Low
Color of muscle tissue Dark or Red Pale or White
Fatigue Slow to fatigue Fast to fatigue
Functional use of muscle Posture, walking (constant) Jump, sprinting (rare)

FURTHER READING - "GOOGLE"

1. Muscle Contraction - SlideShare.

2. Muscle Biochemistry - SIU School of Medicine.
3. Muscle Biochemistry : Structure and Function - Medical Biochemistry.
4. Harper's Illustrated Biochemistry Chapter 49.
5. And many others....