Muscular System: Skeletal Muscle

Muscular System Functions

Body movement
Maintenance of posture
Respiration
Production of body heat
Communication
Constriction of organs and vessels
Heart beat

Properties of Muscle

contractility, excitability, extensibility, elasticity

Contractility

ability of a muscle to shorten with force

Excitability

capacity of muscle to respond to a stimulus

Extensibility

muscle can be stretched to its normal resting length and beyond to a limited degree

Elasticity

ability of muscle to recoil to original resting length after stretched

Muscle Tissue Types

Skeletal, Smooth, Cardiac

Comparison Between Muscle Tissue

Skeletal Muscle
I. Attached to bones; Involuntary
II. Very long cylindrical in length
III. Multiple, peripherally located
IV. Striated
V. Not Capable of Spontaneous Contraction
VI. Function: Body Movement
VII. Fast to Contract

Smooth Muscle
I. Walls of hollow organs, blood vessels, eyes, glands, and skin; Involuntary
II. Spindle shaped
III. Single, centrally located
IV. Not Striated
V. Capable of Spontaneous Contraction
VI. Food movement through digestive tract, emptying of the urinary bladder, regulation of blood diameter,
VII. Slowest To Contract

Cardiac Muscle
I. Heart; Involuntary
II. Cylindrical and branch
III. Single, centrally located
IV. Striated
V. Capable of Spontaneous Contraction
VI. Pumps blood; contraction provide the major force for propelling blood through the blood vessels
VII. Intermediate contraction

Skeletal Muscle

Composed of muscle cells (fibers), connective tissue, blood vessels, nerves
Fibers are long, cylindrical, multinucleated
Tend to be smaller diameter in small muscles
Develop from myoblasts
Numbers remain constant
Striated appearance due to light and dark banding

Connective Tissue Layers

epimysium, perimysium, endomysium, external lamina

External Lamina

Delicate, reticular fibers surrounding the sarcolemma

Endomysium

Loose C.T. with reticular fibers.

Perimysium

Denser C.T. surrounding a group of muscle fibers. Each group called fasciculus

Epimysium

C.T. that surrounds a whole muscle (many fascicles)

Fascia

Connective tissue sheet forms layer under the skin
Holds muscles together and separates them into functional groups
Allows free movements of muscle
Carries nerves (motor neurons, sensory neurons), blood vessels, and lymphatics.
Continuous with connective tissue of tendons and periosteum

Motor Neurons

Stimulate muscle fibers to contract
Axons extend to skeletal muscle fibers through nerves
Axons branch so that each muscle fiber is innervated

Hierarchical Arrangement of The Structural Components of Skeletal Muscle

Epimysium - Perimysium - Endomysium - Muscle fiber - Myofibrils - Sarcomeres - Z-disc - Myosin filaments:

muscle fibers

The individual skeletal muscle cells are known as

endomysium

The individual fibers are surrounded by a CT layer known as

perimysium

Groups of skeletal muscle fibers make up a fasciculus, which is surrounded by a CT layer called

sarcomere

the fundamental contractile unit of striated muscle and consists of overlapping thick and thin filaments that produce a characteristics pattern of light and dark bands

Sarcolemma

cell membrane of the muscle fiber

Transverse - tubules (T - tubules)

Invagination of the muscle cell plasma membrane (sarcolemma), which form a dense interconnecting network that extends throughout the muscle cell cytoplasm.

Importance of T- tubule

Excitation of the by the AP is coupled to Ca ion release from the terminal cisterna of the SR to allow rapid, coordinated mobilization of Ca from internal stores. This results in a coordinated contraction of all the myofibrils.

Role of Transverse (T) Tubules of Sarcoplasmic Reticulum

1. Transmits AP deeply into the muscle fiber to the vicinity of all separate myofibril

2. Cause release of Ca ions in the immediate vicinity of all the myofibril (excitation-contraction coupling)

3. Opens to the exterior

T-Tubules in Skeletal and Cardiac Muscle

Mammalian Skeletal Muscle
: has two T-tubule networks for each sarcomere, located near each end of myosin filament for rapid muscular contraction

Mammalian Cardiac Heart
: has one T-tubule network for each sarcomere, located at the level of the Z disc

Calcium Pump

removes Ca ions from the myofibrillar fluid

Calsequestrin

protein in the SR for storage of calcium ions

Sarcoplasm

Intracellular matrix which suspends the myofibril inside the muscle fiber

: Contains large quantities of K, Mg., PO4, protein, mitochondria

Sarcoplasmic Reticulum

An internal membrane system of the muscle cell, which stores Ca ions that is released during excitation contraction coupling.

: In Skeletal - extremely dense; is prominent
: In Cardiac - less dense
: In Smooth - fairly prominent or relatively sparse i

Membrane contains Ca ATPase (pumps), which transport Ca from intracellular fluid into the SR interior, keeping intracellular Ca low.

Within the SR, Ca is bound loosely to calsequestrin, to be released upon depolarization

How does the SR function?

In Skeletal Muscle - ECF Ca+ Dependent
: Ca release from the SR is coupled to depolarization of the T-tubule membrane so that the excitation of the T-tubule system leads to Ca release from the SR depends entirely on depolarization of the T-tubule membrane.

In Cardiac Muscle - Ca+ Induced Ca+ Release
: increase in cytoplasmic Ca ions causes the rapid release of more Ca ions from the SR (calcium induced Ca ions release)

Terminal Cisternae

Sac-like ends of the SR in skeletal and Cardiac muscle which serves as storage site for Ca ions that are released during excitation-contraction coupling.

Myofibril

Small, longitudinal contractile filament within a muscle cell or fiber
: Contractile Organelles of Myofiber
: Contains 6 types of protein

o Contractile Proteins
o Regulatory Proteins
o Accessory Proteins

Contractile Proteins

Large, polymerized protein molecules responsible for the actual muscle contraction.

: Myosin filament and Actin Filament
: Less myosin, more actin; ratio - 1:2)

Actin (Thin) Myofilaments (Light band)

: I band (isotropic band) from Z disks to ends of thick filaments
: Has Z disc (dark line)

Has 3 types of Proteins:
o Actin
o Tropomyosin
o Troponin

: Two strands of Fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere.

: Fibrous Actin - composed of G actin monomers each of which has an active site

: Actin site can bind myosin during muscle contraction.

Myosin (Thick) Myofilament (Dark band)

: A band (anisotropic band) length of thick filaments

: Has H line (light line) region in A band where actin and myosin do not overlap

: M line: middle of H zone; delicate filaments holding myosin in place

: Elongated myosin molecules shaped like golf clubs

Regulatory Protein

tropomyosin and troponin
: act like a switch to determine when the fiber can contract and when it cannot

Troponin

: Has strong affinity for calcium ion which initiates the contractile process

: Regulatory protein that permits cross bridge formation when it binds Ca

: composed of three subunits:
o one that binds to actin
o a second that binds to tropomyosin
o a third that binds to calcium ions.

: Spaced between the ends of the tropomyosin molecules in the groove between the F actin strands.

Tropomyosin

: elongated protein winds along the groove of the F actin double helix.

The Tropomyosin - Troponin Complex

· Regulates the interaction between active sites on G actin and myosin.

· Inhibits or physically covers the actin sites on the normal actin filament of the relaxed

· Sites cannot attach to the head of the myosin filament to cause contraction

· Has inhibitory effect on muscle contraction but could be inhibited by the presence of calcium ions

Accessory Proteins

Titin and Nebulin

Titin

Biggest protein known (25,000 aa)
Elastic
Stabilizes position of contractile filaments
Return to relaxed location

Nebulin

Inelastic giant protein
Alignment of Actin & Myosin

Sarcomere

portion of the myofibril that lies between two successive Z discs.

Z disk

o Filamentous network of protein.
o Serves as attachment for actin myofilaments
o Striated appearance
o Unit of contraction
o The thin filaments are attached to the Z-lines by alpha actinin, which is a major component of isolated Z disk.

Components of an Individual Sarcomere

I (isotropic) band
A (anisotropic) band
Z lines
H zone
M-line (band)
Thick and Thin Filaments

I (isotropic) band

is a light band composed of thin filaments only

A (anisotropic) band

is a dark band that corresponds to the region of overlap between the thick and thin filament

Z lines

bisect the I band and indicate the borders of the individual sarcomeres.

H zone

corresponds to the center region of the thick filament, which contains the tails, but not the heads, of the myosin molecules.

: Thus, no cross-bridges can be formed

M-line (band)

contains proteins the at link the thick filaments together to maintain their position

Thick and Thin Filaments

composed of a collection of individual proteins.

Components:
Thick Filaments - Myosin
Thin Filaments - Actin, Tropomyosin, and Troponin

Physiology of Skeletal Muscle

: Nervous system controls muscle contractions through action potential

: Resting Membrane Potentials - -70mv

: Inside the cell there are more negative due to accumulation of large protein molecules.

: Outside the cell more positive and more Na+ on outside than inside

: Na/K pump maintains this situation.

Types of Ion Channels

1. Ligand-Gated Channel
: Gate is closed until neurotransmitter attaches to receptor molecule

2. Voltage-Gated Channel
: Open and close in response to small voltage changes across plasma membrane

Ligands

- are molecules that bind to receptors

Neurotransmitter

- substance released from a presynaptic membrane that diffuses across the synaptic cleft and stimulates (or inhibits the production of an action potential in the postsynaptic membrane

Types of Voltage Gated Ion Channels

1. Na+ Voltage Gated Channel
2. K+ Voltage Gated Channel

Na+ Voltage Gated Channel

· Has Two Gates

A Activation Gate
o opens and closes outward
o Opens: allows entry of Na ions

B. Inactivation Gate
o opens and closes inward
o Closed: prevent entry of Na ions

K+ Voltage Gated Channel

· Has One Gate
o Opens and closes outward
o Opened: allow outward movement of K ions

Resting Membrane Potential (RMP)

· Na channels and some but not all, K channels are closed.

· Few K ions diffuse down the gradient through the open K gradient, making the outside of the cell membrane positively charged comp

Phases of Action Potentials in Skeletal muscle

1. Depolarization
2. Repolarization
3. Return to RMP by NA-K Pump

Depolarization

: Inside of plasma membrane becomes less negative.

: If change reaches threshold, depolarization occurs

: Na channels are open

: Few Na diffuse down their concentration gradient through the open Na channels, making the inside of the cell membrane positively charged compared to the outside

Repolarization

Returns to resting membrane potential.

The membrane potential drops lower than its original resting potential, then rebounds.

This is because Na plus K together are higher, but then Na/K pump restores the resting potential

Na channels are closed, and Na ions' movement into the cells stops.

More K channels open. K ions' movement out of the cell increases, making the outside of the cell membrane positively charged compared to the inside

Two Theories of Muscle Contraction

1. Walk Along Theory of Contraction
2. Sliding Filaments Theory of Contraction

Walk Along Theory of Contraction

explains how activated actin filament and the myosin cross-bridges interact to cause contraction.

: When myosin head attaches to an active site, the head tilts automatically toward the arm that is dragged along the actin filament.

Sliding Filaments Theory of Contraction

refers to the generation of contractile force by the interaction of thick and thin filaments, causing therefore to slide between each other

: Myosin "walks down" an actin fiber towards Z-line

What Is Excitation- Contraction Coupling?

The process by which the excitation of a muscle cell is coupled to increase in cytoplasmic Ca ions concentration and muscle contraction.

: The increase in cytoplasmic Ca ions concentration initiates muscle contraction by interacting with regulatory proteins, such as troponin in skeletal and cardiac muscle or calmodulin in smooth muscle.

Mechanism where an action potential causes muscle fiber contraction involves:

[1] Sarcolemma
[2] Transverse (T) tubules: invaginations of sarcolemma
[3] Terminal cisternae
[4] Sarcoplasmic reticulum: smooth ER
[5] Triad: T tubule, two adjacent terminal cisternae
[6] Ca2+
[7] Troponin

Steps In Excitation-Contraction Coupling in Skeletal Muscle

1. An Action Potential travels along a motor nerve to its ending on muscle fibers

2. At each ending, the nerve secretes a small amount of acetylcholine (neurotransmitter)

3. The acetylcholine acts on a local area of the muscle fiber membrane to open multiple-gated channels through which protein molecules floating in the membrane

4. Opening of the Acetylcholine - gated channels allow large quantities of Na ions to flow to the interior of the muscle fiber membrane (This initiates an Action Potential in the muscle fiber)

5. The AP travels along the muscle fiber membrane in the same way that AP travels along nerve membrane

6. The AP depolarizes the muscle membrane, and much of the AP electricity also travels deeply within the muscle fibers. Here, it causes the sarcoplasmic reticulum to release large quantities of calcium anions that have been stored within the reticulum

7. The calcium ion initiates attractive force between the actin and myosin filaments causing, to slide alongside each other, which is the contractile process.

8. After a fraction of a second, the calcium ions are pumped back into the SR by a calcium pump. The removals of the calcium ions from the myofibril cause muscle contraction to cease.

During relaxation, what happened to the sarcomere length?

sarcomeres lengthen because of some external force, like contraction of Antagonistic Muscles

Relaxed State

Ends of the actin filament derived from two successive Z discs barely begin to overlap one another, while at the same time lying adjacent to the myosin filament

Contracted State

Actin Filaments have been pulled inward among the myosin filaments, so that their ends now overlap one another to a major extent. Also, the Z discs have been pulled by the actin filament up to the ends of the myosin filament.

Actin, Myosin and Sarcomere during Contraction

: Actin myofilaments sliding over myosin to shorten sarcomeres.

: Actin and myosin do not change length. Shortening sarcomeres responsible for skeletal muscle contraction

Three Major Roles of ATP In Muscle Function

[1] ATP provides energy for generation of contractile force,
when it is hydrolyzed by the globular heads of the myosin molecules

[2] ATP binds to the head of the myosin molecule, reducing the affinity of the CB for the active sites.

[3] ATP also provides energy for ion pump,
: to maintain normal ionic gradients across the cell and to pump Ca out of the cell or back into the SR.

Sources of Energy for Muscle Contraction

1. Phosphorylation (Anaerobic Respiration)
2. Glycogen (Creatine phosphate)
3. Oxidative Metabolism (Aerobic respiration)

Phosphorylation (Anaerobic Respiration)

Occurs in absence of oxygen and results in breakdown of glucose to yield ATP and lactic acid

: Used to reconstitute the ATP
: Carries a high energy bond similar to the bonds of ATP
: Causes maximal contraction for only 5 to 8 seconds

Glycogen (Creatine phosphate)

During resting conditions stores energy to synthesize ATP

: Used to reconstitute both ATP and phosphocreatine
: Stored in the muscle cell
: Enzyme breakdown glycogen to pyruvic acid and lactic acid. Liberate energy that is used to convert ADP to ATP (process called glycolysis)

Glycolysis Mechanism in Two-Fold:

First:
Glycolytic reaction can occur even in the absence of oxygen, so that muscle contraction can be sustained for many seconds and sometimes up to a minute even when oxygen is not available

Second:
The rate of formation of ATP is about 2 ½ times as rapid as ATP formation when the cellular foodstuffs react with oxygen

Oxidative Metabolism (Aerobic respiration)

Requires oxygen and breaks down glucose to produce ATP, carbon dioxide and water

· More efficient than anaerobic

· Combining of oxygen with the various cellular foodstuffs (carbohydrates, fat, and protein) to liberate ATP

· More than 95% of all energy used by the muscle for sustained, long term contraction is derived from this source

· For extremely long-term maximal muscle activity over a period of many hours - by far the greatest proportion of energy come from fat, but for period lasting 2 to 4 hours, as much as one half of the energy can come from the stored glycogen before the glycogen is depleted

Oxygen Debt

Oxygen taken in by the body, above that required for resting metabolism after exercise. ATP

· Produced from anaerobic sources contributes

Muscle Twitch

· A single, brief contraction of the muscle that occurs in response to a single threshold or suprathreshold

· Muscle contraction in response to a stimulus that causes action potential in one or more muscle fiber

· Composed of:
a) Latent or Lag Period
b) Period of Contraction
c) Period of Relaxation

Slow-Twitch Muscle Fibers (High-Oxidative)

· (type I fibers), are oxidative skeletal muscle fibers that exhibit a slower velocity than fast-twitch fibers

· Contract more slowly, smaller in diameter, better blood supply, more and bigger mitochondria, more fatigue resistant than fast-twitch, large amount of myoglobin.

· Postural muscles, more in lower than upper limbs. Dark meat of chicken.

· Aerobic, more myoglobin and no hypertrophy

· Has steady power and endurance

Fast-Twitch Fibers (Low-Oxidative)

· Glycolytic muscle fibers that have a high velocity of contraction

· Fast glycolytic fibers are also called type II B fibers, to distinguish them from type II A (fast oxidative) fibers, which have high oxidative and glycolytic capabilities (found in some mammals but are not abundant in hum an).

· Respond rapidly to nervous stimulation, contain myosin that can break down ATP more rapidly than that in Type I, less blood supply, fewer and smaller mitochondria than slow twitch

· Lower limbs in sprinter, upper limbs of most people.

· White meat in chicken.

· Velocity of contraction of slow-twitch and fast-twitch muscle fibers is determined by the rate of ATP hydrolysis by the myosin molecule.

· Most skeletal muscle are mixture of slow-twitch and fast twitch fibers.

· Anaerobic

· Has explosive power but fatigues easily

· More actin and myosin; more sarcomeres and more myofibrils and muscle hypertrophy

Distribution of Fast-Twitch and Slow-Twitch

· Most muscles have both but varied for each muscle

· Skeletal Muscle Fiber Types
o Slow Oxidative (RED)
o Fast Glycolytic (WHITE)
o Fast Oxidative (WHITE)

Slow Oxidative (RED)

§ Many Mitochondria
§ Much Myoglobin

Fast Glycolytic (WHITE)

§ Large Diameter
§ Large Glycogen Stores
§ Large Calcium pumping ability

Fast Oxidative (WHITE)

§ Small Diameter
§ Many Mitochondria
§ Fast Myosin ATPase

Isometric Contraction

· Muscle does not shorten during contraction

· Contraction in which the external length of the muscle does not change because the force being generated by the muscle is insufficient to move the load to which it is attached.

Isotonic Contraction

· Muscle does retention with tension on the muscle remaining constant

· Contraction in which a muscle shortens while it exerts a constant force that matches the load being lifted by the muscle.

Change in Length but Tension Constant

Concentric:
overcomes opposing resistance and muscle shortens; The muscle shortens as it moves the load

Eccentric:
tension maintained but muscle lengthens; The muscle lengthens as it resists the load

Motor Unit

a single motor nerve fiber that innervates all the muscle fiber

Stimulus Strength and Muscle Contraction

All-or-none law for muscle fibers
: Contraction of equal force in response to each action potential

[1] Sub-threshold stimulus:
no action potential; no contraction

[2] Threshold stimulus:
action potential; contraction

[3] Stronger than threshold;
action potential; contraction equal to that with threshold stimulus

Stimulus Strength and Skeletal Muscle Contraction

Strength of skeletal muscle contraction is graded: ranges from weak to strong depending on stimulus strength

A. Submaximal Stimuli
Tension generation of progressive motor units resulted to tension (summation) - producing the maximum tension is generated

B. Maximal Stimulus

C. Supramaximal Stimuli
Maximum Tension Generated by Muscles

Summation

Adding together of individual twitch contraction to increase the intensity of overall muscle contraction

· Occurs in two ways:
A. Multiple Fiber Summation
B. Frequency Summation

Multiple Fiber Summation

Also called as Multiple Motor Unit Summation

: Due to increasing the number of motor unit contracting simultaneously

: Strength of contraction depends upon recruitment of motor units.

: Muscle has many motors units

Frequency Summation

· Also called as Multiple-Wave Summation

· As the frequency of action potentials increase, the frequency of contraction increases

· Increasing the frequency of contraction

· Lead to tetanization (successive contractions are so rapid that the Individual muscle twitches literally fuse together and the contraction appears to be completely smooth and continuous.

· Due to enough Calcium ions are maintained in the sarcoplasm even Between AP, so that full contractile state is sustained without allowing relaxation between the AP.

Muscle Fatigue

Prolong and strong contraction of a muscle
: Decreased capacity to work and reduced efficiency of performance

Causes of Fatigue:

1. Build-up of metabolic products in the tissue owing to insufficient blood flow

2. Transmitter depletion at the NMJ

3. Insufficient supply of nutrients to maintain contraction (depletion of muscle glycogen)

Fatigue Types

a) Psychological: depends on emotional state of individual

b) Muscular: results from ATP depletion

c) Synaptic: occurs in NMJ due to lack of acetylcholine

Tetanic Contraction or Tetanus

: Maintained contraction of a skeletal muscle owing to the continuous excitation of muscle fiber

Types:

o Incomplete tetanus:
muscle fibers partially relax between contractions

o Complete tetanus:
no relaxation between contractions