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9. Muscular System:Histology and Physiology

Prepared by: Mirza Anwar Baig M.Pharm (Pharmacology)

Anjuman I Islam's Kalsekar Technical Campus,School of Pharmacy.

New Panvel,Navi Mumbai

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Contents:1.Cardiac muscles2.Smooth muscles3.Skeletal muscles4.Neuromuscular transmission and contraction of skeletal muscle5.Energy metabolism in the muscle6.Types of muscle contractions7.Muscle tone

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Functions of Muscular System

1.Body movement (Locomotion)2.Maintenance of posture3.Respiration

Diaphragm and intercostal contractions

4.Communication (Verbal and Facial)5.Constriction of organs and vessels

1.Peristalsis of intestinal tract2.Vasoconstriction of b.v. and other structures (pupils)

6.Heart beat 7.Production of body heat (Thermogenesis)

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Properties of Muscle

1.Excitability: capacity of muscle to respond to a stimulus

2.Contractility: ability of a muscle to shorten and generate pulling force

3.Extensibility: muscle can be stretched back to its original length

4.Elasticity: ability of muscle to recoil to original resting length after stretched

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Types of Muscle

• Skeletal– Attached to bones– Makes up 40% of body weight– Responsible for locomotion, facial expressions, posture,

respiratory movements, other types of body movement– Voluntary in action; controlled by somatic motor neurons

• Smooth– In the walls of hollow organs, blood vessels, eye, glands,

uterus, skin– Some functions: propel urine, mix food in digestive tract,

dilating/constricting pupils, regulating blood flow, – Controlled involuntarily by endocrine and autonomic nervous

systems• Cardiac

– Heart: major source of movement of blood– Autorhythmic– Controlled involuntarily by endocrine and autonomic nervous

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Connective Tissue Sheaths

• Connective Tissue of a Muscle

– Epimysium. Dense regular, surrounding entire muscle

• Separates muscle from surrounding tissues and organs

•Connected to the deep fascia

– Perimysium. Collagen and elastic fibers surrounding a group of muscle fibers called a fascicle

•Contains b.v and nerves

– Endomysium. Loose connective tissue that surrounds individual muscle fibers

•Also contains b.v., nerves, and satellite cells (embryonic stem cells function in repair of muscle tissue

• Collagen fibers of all 3 layers come together at each end of muscle to form a tendon or aponeurosis. 6

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Nerve and Blood Vessel Supply

• Motor neurons– stimulate muscle fibers to contract– Neuron axons branch so that each muscle fiber

(muscle cell) is innervated– Form a neuromuscular junction (= myoneural

junction)

• Capillary beds surround muscle fibers– Muscles require large amts of energy– Extensive vascular network delivers necessary

oxygen and nutrients and carries away metabolic waste produced by muscle fibers

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Basic Features of a Skeletal Muscle

• Muscle attachments– Most skeletal muscles

run from one bone to another

– One bone will move – other bone remains fixed

• Origin – less movable attach- ment

• Insertion – more movable attach- ment

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Skeletal Muscle Structure

• Composed of muscle cells (fibers), connective tissue, blood vessels, nerves

• Fibers are long, cylindrical, and multinucleated

• Tend to be smaller diameter in small muscles and larger in large muscles. 1 mm to 4 cm in length

• Develop from myoblasts; numbers remain constant

• Striated appearance

• Nuclei are peripherally located10

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Muscle Fiber Anatomy• Sarcolemma - cell membrane

– Surrounds the sarcoplasm (cytoplasm of fiber)• Contains many of the same organelles seen in other cells• An abundance of the oxygen-binding protein myoglobin

– Punctuated by openings called the transverse tubules (T-tubules)• Narrow tubes that extend into the sarcoplasm at right

angles to the surface• Filled with extracellular fluid

• Myofibrils -cylindrical structures within muscle fiber– Are bundles of protein filaments (=myofilaments)

• Two types of myofilaments1. Actin filaments (thin filaments)2. Myosin filaments (thick filaments)

– At each end of the fiber, myofibrils are anchored to the inner surface of the sarcolemma

– When myofibril shortens, muscle shortens (contracts) 11

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Sarcoplasmic Reticulum (SR)• SR is fluid-filled system of membranous sacs

– runs longitudinally and surrounds each myofibril– Form chambers called terminal cisternae on either side of the T-tubules

• A single T-tubule and the 2 terminal cisternae form a triad

• SR stores Ca++ when muscle not contracting– When stimulated, calcium released into sarcoplasm

– SR membrane has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR after contraction

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Sarcoplasmic Reticulum (SR)

Figure 9.513

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Parts of a Muscle

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Sarcomeres: Z Disk to Z Disk

• Sarcomere repeating functional units of a myofibril– About 10,000 sarcomeres per

myofibril, end to end– Each is about 2 µm long

• Differences in size, density, and distribution of thick and thin filaments gives the muscle fiber a banded or striated appearance.– A bands: a dark band; full length of

thick (myosin) filament– M line: protein to which myosins

attach– H zone: thick but NO thin filaments– I bands: a light band; from Z disks to

ends of thick filaments• Thin but NO thick filaments• Extends from A band of one

sarcomere to A band of the next sarcomere

– Z disk: filamentous network of protein. Serves as attachment for actin myofilaments

– Titin filaments: elastic chains of amino acids; keep thick and thin filaments in proper alignment

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Structure of Actin and Myosin

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Myosin (Thick) Myofilament

• Many elongated myosin molecules shaped like golf clubs.

• Single filament contains roughly 300 myosin molecules• Molecule consists of two heavy myosin molecules

wound together to form a rod portion lying parallel to the myosin myofilament and two heads that extend laterally.

Myosin heads:• Can bind to active sites on the actin molecules to form

cross-bridges. (Actin binding site)• Attached to the rod portion by a hinge region that can

bend and straighten during contraction. • Have ATPase activity: activity that breaks down

adenosine triphosphate (ATP), releasing energy. • Part of the energy is used to bend the hinge region of

the myosin molecule during contraction.

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Structure and Arrangement of Myosin Molecules Within Thick Filament

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Actin (Thin) Myofilaments

• Thin Filament: composed of 3 major proteins1. F (fibrous) actin2. Tropomyosin3. Troponin

• Two strands of fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere.– Composed of G actin

monomers each of which has a myosin- binding site (see yellow dot)

– Actin site can bind myosin during muscle contraction.

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

• Troponin is composed of three subunits: – Tn/ A : binds to actin– Tn/ T :binds to tropomyosin,– Tn/ C :binds to calcium ions.

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Role of Calcium in Cross-Bridge Formation

• During relaxed state

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Role of Calcium in Cross-Bridge Formation

• Excited

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24CROSS-BRIDGE CYCLE24

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Changes in Banding Pattern During Shortening

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Sliding Filament Mechanism

Cross bridge interaction between actin and myosin brings about

muscle contraction by means of the sliding filament mechanism.

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Sliding Filament Mechanism

• Increase in Ca2+ starts filament sliding• Decrease in Ca2+ turns off sliding

process• Thin filaments on each side of

sarcomere slide inward over stationary thick filaments toward center of A band during contraction

• As thin filaments slide inward, they pull Z lines closer together

• Sarcomere shortens 27

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Sliding Filament Mechanism

• All sarcomeres throughout muscle fiber’s length shorten simultaneously

• Contraction is accomplished by thin filaments from opposite sides of each sarcomere sliding closer together between thick filaments.

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Power Stroke• Activated cross bridge bends toward

center of thick filament, “rowing” in thin filament to which it is attached– Sarcoplasmic reticulum releases Ca2+ – Myosin heads bind to actin– Hydrolysis of ATP transfers energy to

myosin head and reorients it– Myosin heads swivel toward center of

sarcomere (power stroke)– ATP binds to myosin head and detaches

it from actin29

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Contraction- Relaxation Steps Requiring ATP

• Splitting of ATP by myosin ATPase provides energy for power stroke of cross bridge

• Binding of fresh molecule of ATP to myosin lets bridge detach from actin filament at end of power stroke so cycle can be repeated

• Active transport of Ca2+ back into sarcoplasmic reticulum during relaxation depends on energy derived from breakdown of ATP

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Neuromuscular Junction• Region where the motor neuron stimulates the

muscle fiber• The neuromuscular junction is formed by :

1. End of motor neuron axon (axon terminal)• Terminals have small membranous sacs (synaptic

vesicles) that contain the neurotransmitter acetylcholine (ACh)

2. The motor end plate of a muscle• A specific part of the sarcolemma that contains

ACh receptors• Though exceedingly close, axonal ends and

muscle fibers are always separated by a space called the synaptic cleft

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Motor Unit: The Nerve/ Muscle Functional Unit

Figure 9.12 (a)

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Motor Unit: The Nerve/ Muscle Functional Unit

• A motor unit is a motor neuron and all the muscle fibers it supplies

• The number of muscle fibers per motor unit can vary from a few (4_6) to hundreds (1200_1500)

• Muscles that control fine movements (fingers, eyes) have small motor units

• Large weight/ bearing muscles (thighs, hips) have large motor units

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Motor Unit: The Nerve-Muscle Functional Unit contd...

• Muscle fibers from a motor unit are spread throughout the muscle– Not confined to one fascicle

• Therefore, contraction of a single motor unit causes weak contraction of the entire muscle

• Stronger and stronger contractions of a muscle require more and more motor units being stimulated (recruited)

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Neuromuscular Junction

Figure 9.7 (a-c)

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Generation of action potential

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Muscle contraction

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Major Events in Neuromuscular Transmission

• Motor neuron depolarization causes action potential to travel down the nerve fiber to the neuromuscular junction (1).

• Depolarization of the axon terminal causes an influx of Ca2+ (2) which triggers fusion of the synaptic vesicles (3) and release of neurotransmitter (Acetylcholine; ACh) (4).

• ACh diffuses across the synaptic cleft and binds to post/ synaptic ACh receptor (AChR) located on the muscle fiber at the motor end/ plate (5).

• Binding of ACh to AChRs opens the channels causing an influx of Na (5), depolarization of the sarcolemma that travels down the t/ tubules (6) and ultimately causes the release of Ca2+ from the sarcoplasmic reticulum / CONTRACTION.

• Unbound ACh in synaptic cleft defuses away or is hydrolyzed (inactivated) by acetylcholinesterase (AChE) (7).

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Muscle Response to Strong Stimuli

•Muscle force depends upon the number of fibers stimulated– More fibers contracting results in greater muscle tension

•Muscles can continue to contract unless they run out of energy

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How Do Muscles Get Energy?

• Initially, muscles use stored ATP for energy– ATP bonds are broken to

release energy– Only 4–6 seconds

worth of ATP is stored by muscles

• After this initial time, other pathways must be utilized to produce ATP 42

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Skeletal muscle energy metabolism

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1. Creatine Phosphate (high-energy molecule)

• Muscle cells store CP

• CP transfers energy to ADP, to regenerate ATP by direct phosphorylation of ADP

• Creatine synthesize in liver,pancrease,kidneys

• The enzyme creatine kinase forms CP from creatine and ADP

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2.Anaerobic Respiration• Anaerobic glycolysis and

lactic acid formation– Reaction that breaks

down glucose without oxygen

– Glucose is broken down to pyruvic acid to produce some ATP

– Pyruvic acid is converted to lactic acid

• This reaction is not as efficient, but is fast– Huge amounts of glucose

are needed– Lactic acid produces

muscle fatigue45

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3.Aerobic Respiration

• Glucose is broken down to carbon dioxide and water, releasing energy (ATP)

• This is a slower reaction that requires continuous oxygen

• A series of metabolic pathways occur in the mitochondria

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Muscle Fatigue & Oxygen Debt

• When a muscle is fatigued, it is unable to contract even with a stimulus

• Common cause for muscle fatigue is oxygen debt– Oxygen must be “repaid” to

tissue to remove oxygen deficit– Oxygen is required to get rid

of accumulated lactic acid• Increasing acidity (from lactic

acid) and lack of ATP causes the muscle to contract less

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Smooth Muscle• Located in the blood vessels, the

respiratory tract, the iris of the eye, the gastro-intestinal tract

• The contractions are slow and uniform

• Functions to alter the activity of various body parts to meet the needs of the body at that time

• Is fatigue resistant

• Activation is involuntary

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Smooth Muscle

• Cells are not striated• Fibers smaller than those

in skeletal muscle• Spindle-shaped; single,

central nucleus• More actin than myosin• No sarcomeres

– Not arranged as symmetrically as in skeletal muscle, thus NO striations.

• Dense bodies instead of Z disks – Have noncontractile

intermediate filaments49

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Smooth Muscle

Figure 9.24

• Grouped into sheets in walls of hollow organs• Longitudinal layer – muscle fibers run parallel to organ’s long axis• Circular layer – muscle fibers run around circumference of the organ

• Both layers participate in peristalsis

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Cardiac Muscle• Has characteristics of both skeletal

and smooth muscle

• Functions to provide the contractile

activity of the heart

• Contractile activity can be gradated

(like skeletal muscle)

• Is very fatigue resistant

• Activation of cardiac muscle is

involuntary (like smooth muscle)

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Cardiac Muscle

• Found only in heart where it forms a thick layer called the myocardium

• Striated fibers that branch

• Each cell usually has one centrally-located nucleus

• Fibers joined by intercalated disks

– IDs are composites of desmosomes and gap junctions

– Allow excitation in one fiber to spread quickly to adjoining fibers

• Under control of the ANS (involuntary) and endocrine system (hormones)

• Some cells are autorhythmic– Fibers spontaneously contract ( Pacemaker cells) 52

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Cardiac Muscle Tissue

Figure 10.10a53

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Cardiac Muscle and Heart Function•Cardiac muscle fibers are striated – sarcomere is the functional unit

• Fibers are branched; connect to one another at intercalated discs. The discs contain several gap junctions

•Nuclei are centrally located•Abundant mitochondria•SR is less abundant than in

skeletal muscle, but greater in density than smooth muscle

•Sarcolemma has specialized ion channels that skeletal muscle does not – voltage/ gated Ca2+ channels

• Fibers are not anchored at ends; allows for greater sarcomere shortening and lengthening 54

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How are cardiac contractions started? Cardiac conduction system• Specialized muscle cells “pace”

the rest of the heart; cells contain less actin and myosin, are thin and pale microscopically

• Sinoatrial (SA) node; pace of about 65 bpm

• Internodal pathways connect SA node to atrioventricular (AV) node

• AV node could act as a secondary pacemaker; autorhythmic at about 55 bpm

• Bundle of His• Left and right bundle branches• Purkinje fibers; also

autorhythmic at about 45 bpmALL CONDUCTION FIBERS CONNECTED TO MUSCLE FIBERS THROUGH GAP JUNCTIONS IN THE INTERCALATED DISCS

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Muscle tone:• Muscle tone (tonos=tension), a small amount of tautness

or tension in the muscle due to weak, involuntary contractions of its motor units.

• Muscle tone keeps skeletal muscles firm, but it does not result in a force strong enough to produce movement.

For example, 1. Upright position of head : when the muscles in the back of

the neck are in normal tonic contraction, they keep the head upright and prevent it from slumping forward on the chest.

2. Gastrointestinal tract: where the walls of the digestive organs maintain a steady pressure on their contents.

3. Walls of blood vessels: plays a crucial role in maintaining blood pressure.

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Disorders of Muscle tone:

• Hypotonia refers to decreased or lost muscle tone.• Such muscles are said to be flaccid.

• Flaccid muscles are loose and appear flattened rather than rounded.

• Certain disorders of the nervous system and disruptions in the balance of electrolytes (especially sodium, calcium, and, to a lesser extent, magnesium) may result in flaccid paralysis, which is characterized by loss of muscle tone, loss or reduction of tendon reflexes, and atrophy (wasting away) and degeneration of muscles.

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Hypertonia refers to increased muscle tone and is

expressed in two ways: spasticity or rigidity.

1.Spasticity is characterized by increased muscle tone (stiffness)

• Certain disorders of the nervous system and electrolyte disturbances such as those previously noted may result in spastic paralysis, partial

paralysis in which the muscles exhibit spasticity.

2. Rigidity refers to increased muscle tone in which reflexes are not affected.

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Types of Muscle Contractions

• Isometric contractions– Tension in the muscles

increases– The muscle is unable to

shorten or produce movement

• Isotonic contractions– Myofilaments are able to

slide on each other during contractions

– The muscle shortens and movement occurs

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