BAI GIANG HE CO XUONG (musculoskeletal system)

Locomotor/Musculoskeletal systemHệ vận động- Sinh lý cơ và xương In this chapter, students will learn: •Components of the musculoskeletal system •Basic of how musculoskeletal system gene

Locomotor/Musculoskeletal system

(Hệ vận động- Sinh lý cơ và xương)

In this chapter, students will learn:

•Components of the musculoskeletal system

•Basic of how musculoskeletal system generates motion

•Structure of skeletal muscle: muscle fiber, myofibrils, actin and myosin filaments

• Structures of a sarcomere

•The movements of actin and myosin filaments during muscle contraction

•Molecular mechanism of muscle contraction The crossbridge cycle Role of Ca2+ and ATP in muscle contraction

•Motor unit

•muscle twitch and phases of a muscle twitch

•Isotonic and isometric contraction

•muscle fatigue

•ATP production in muscle cells – Oxygen debt

•Structure of bone tissue, bone cells and their function

•Osteoblast, osteocyte, osteoclast and their function

• long bone elongation and bone remodeling

• Structure of smooth muscle and molecular mechanism of smooth muscle

contraction

Specific terms and keywords

• other connective tissue

Cơ tam đầu (co)

http://www.helicon.co.uk/images/samples/C00100.gif

Cơ nhị đầu (giãn)

Muscles and skeletal are main components of locomotor system

– striated/skeletal muscle endoskeletal,

muscles

The musculoskeletal system generates motion for

animals

• Muscles are attached to bones

• Bones are connected by joints

• Muscle contraction allows motion of the bone attached at the joints

• Muscles across joints are arranged in antagonistic

groups allowing motion in different directions

Skeletal muscle – structure and physiology

Structure of a skelelal muscle

• muscle fibers– muscle cell surrounded by sarcolemma: multiple nuclei Cơ tương (chứa

myoglobin), myofibrils, protein filaments

Nhân

Màng sợi cơ

Các sợi cơ trong bó cơ

Structure of a muscle cell

nhân

Sợi cơ

Axon của TB thần kinh vận động

ống T Màng bao cơ

Ti thể

Tơ cơ

Sợi mỏng (actin) Sợi dày

Fig 12.2 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Myofibril and sarcomere

• Thick and thin filaments are orderly arranged (in

a 1:2 ratio) showing striped appearance (hence the name

striated muscle)

• Z line

• M line

• Sarcomere (Đơn vị co cơ): the structure between two neighbouring z lines

A band ( dark band) Z-line

Sarcomere

H zone

myosin

•A band ( dark band): thick

filaments overlapped with thin filaments at the two ends

•H zone: center region of A band where only thick

filaments are present

• I band: structure between A bands where only thin

filaments are present

Structure of a thick filament

• thick filament myosin:

– A myosin molecule is a dimercomposed of two subunits wound together making a “golf stick” shape:

+ Actin-binding site + ATPase site

Fig 12.5 C.L Standfield.2011 Principles of Human Physiology, 4thedition.

Structure of a thin filament

• Thin filament:

– G actin: monomer containing binding site

myosin-– F actin: a strand of G-actin

– 2 F actins are arranged in double helix

forming actin strands found in thin filaments

– 2 regulatory proteins control the

contraction of muslce fiber

• Tropomyosin: long fibrous molecule extending over actin monomers to block the myosin-binding site when muslce is at rest

• Troponin complex consists of 3 subunites:

– One attaches to the actin strand – One binds tropomyosin

– One is the site for reversible binding with Ca2+

Fig 12.5 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Sliding -filament model of muscle contraction

Muscle relaxed : H zone is increased in length

Muscle contracted : H zone is decreased in length

Fig 12.5 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Molecular mechanism of muscle contraction: overview

• 7 steps

• T- Tubules (transverse

tubules): membranous tubules formed by deep invagination of sarcolemma into the cytoplasm

of the muscle cell

• T- tubules transmit action potential

• High Ca2+ concentration in lumen of the SR (sarcoplasmic reticulum) when muscle relaxed

Fig 12.8 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Molecular mechanism of muscle contraction , step 1:

acetylcholine release and the generation of action potential in

the motor end plate of neuromuscular junction

• Neuromuscular junction:

- presynaptic motor neuron (synaptic vesicles containing Acetylcholine-ACh)

- postsynaptic muscle cell membrane –motor end plate (ACh receptors)

- ACh-gated Na+ channels on motor end plate

- Acetylcholinesterase

http://mynotes4usmle.tumblr.com/post/34773331063/houseofmind-the-neuromuscular-junction-nmj

Molecular mechanism of muscle contraction, step 2-3:

action potential propagates down T-tubules triggering

Ca2+ release from sarcoplasmic reticulum

• Voltage-sensitive DHP receptor in T tubules

• Ryanodine receptors in the

SR membrane associate with calcium channels

• AP -> DHP receptor-> open Ca2+ channels-> Ca2+

release from SR to the cytosol

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Molecular mechanism of muscle contraction, step 4:

how Ca2+ function in muscle contraction

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Molecular mechanism of muscle contraction, step 4:

the crossbridge cycle

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Step 6-7: muscle fiber relaxes after crossbridge cycles

Fig 12.8 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Rigor mortis ( Sự cứng cơ khi chết)

– No more ATP production – Ca 2+ are still available in the cytosol

Neurotoxins and muscle paralysis

• Spastic paralysis

( Liệt co cứng ): stiffness of the muscles and muscular spasms

+ insecticides, chemical weapons inhibit AChE

• Flaccid paralysis

(Liệt mềm nhũn ): a weakness

or lack of muscle tone

+ Snake venom + Curare

+ Botulinum (Clostridium botulinum)- botulism

• Botox

http://mynotes4usmle.tumblr.com/post/34773331063/houseofmind-the-neuromuscular-junction-nmj

Regarding muscle contraction process,

What would happen if:

1 Na+ ion channels were blocked and there was no movement of Na+

through membrane of muscle cells ?

2 There was an insufficient amount of ATP available in the muscle cells ?

3 There were an sufficient amount of ATP and an excess amount of

Ca2+ available in the cytosol of muscle fibers ?

Muscle twitch and its phases

• A twitch is the mechanical response of an individual muscle cell, a motor unit, or a whole

muscle to a single action potential

– Lag/latent peroid (Giai đoạn tiềm tàng ): 2ms: delay time between the action potential in the muscle cell and the start of contraction ( release of Ca 2+ )

– contraction phase (Giai đoạn cơ co):

10-100 ms: time between the end of

latent period and the peak of muscular tension: increasing cytosolic Ca2+ levels, increasing active actin-myosin crossbridges

– relaxation phase ( Giai đoạn cơ giãn) :

decreasing cytosolic Ca2+ levels, decreasing active actin-myosin crossbridges

measured in unit of mass (gram (g)

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Motor unit ( Đơn vị vận động)

• Motor unit :

– A motor neuron and all the

muscle fibers innervated by that neuron are collectively

defined as a motor unit

http://academic.wsc.edu/faculty/jatodd1/351/motor_unit.jpg

Isometric and isotonic contraction

• isometric contraction (Co cơ đẳng trường):

- Tension created, but muscle does not shorten as the load is greater than the

force generated – Unchanged muscle length

• isotonic contraction ( Co cơ đẳng trương):

– Created tension is equal or greater than the load

– The muscle shortens, muscle length changes

Co cơ đẳng trương

Co cơ đẳng trường

Fig 12.13 C.L Standfield.2011 Principles of Human Physiology,

4 th edition.

Effects of load on peak tension in an isotonic twitch

Fig 12.14 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Factor affecting the force generated by individual muscle fibers:

Frequency : certain low stimulus frequency causes treppe

• Occurs at a frequency of muscle stimulation where independent twitches follow one another closely such that the peak tension rises in stepwise fashion with each twitch until

eventually it reaches a constant level

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Treppe

Factor affecting the force generated by individual muscle fibers:

Frequency : high stimulus frequency causes summation and tetanus

• High Ca2+ level in the cytosol

Factors affecting the force generated by individual muscle fibers:

Fiber diameter and fiber length

• Force-generating capacity of a muscle fiber depends on

– fiber’s diameter – the length of muscle fiber (created by length of the sarcomeres, not by the number of sarcomeres in series) at the onset of contraction

• Muscle at optimum length generates greatest force

Increase in the number of active motor units increases

force for whole muscles: recruitment

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

The size principle

• Causes of muscle fatigue:

– Precise causes of muscle fatigue are still largely unknown

– Lactic acid accumulation in intensity exercises

high-– Depletion of energy reserves (glycogen) low-intensity exercises

– Neuromuscular fatigue (depletion of acetylcholine release at synapse)

– psychologic fatigue: influence of mental

state and physical condition

ATP production in muscle cells

ensures the steady supply of ATP for very early stages of muscle contraction

creatine kinase

creatine phosphate+ ADP < -> ATP + creatine

• ATP produced by substrate-level phosphorylation and oxidative phosphorylation

– aerobic respiration: moderate exercise

• Glucose 6O2 + 38 ADP + 38 P -> 6CO2 + 6H2O+ 38 ATP

• Effective; glucose, fatty acids and amino acids can be used

• slow

– anaerobic respiration: heavy exercise

• Glucose -> 2 ATP + 2 acid pyruvic

pyruvate -> lactate

• less effective (2ATP)

• Fast

taken into the body after vigorous exercise to restore all systems to their normal states

Types of skeletal muscle fibers

• Muscle fiber types are defined by their speed of contraction and

by the way they produce ATP :

– Slow-twitch muscle fiber ( Sợi cơ chậm) :slow myosin (hydrolize ATP faster)

– Fast-twicht muscle fiber ( Sợi cơ nhanh ): fast myosin (hydrolize ATP faster)

– Glycolytic fibers (referred as ”white muscle”) : few mitochondria, high cytosolic

levels of glycolytic enzymes, lack of myoglobin

– Oxidative fibers (referred as ”red muscle”): rich in mitochondria, high capacity of

producing ATP by oxidative phosphorylation, small in diameter, rich capillary supply, containing myoglobin

• 3 major classes of muscle fibers:

- slow oxidative fibers: slow myosin, high oxidative capacity, smallest diameter, force

- fast glycolytic fibers: fast myosin, high glycolytic capacity, largest diameter, force

- fast oxydative fibers: high oxidative capacity, fast myosin, intermediate diameter,

force

Exercise and muscle building

capacity of muscle fibers, increasing muscle resistance to fatigue, converting some fast glycolytic fibers to fast oxidative fibers:

increases in size and number of mitochondria, increases capillary supply, decrease muscle fiber diameter

• Muscle fiber/cells are postmitotic : muscle cells can not divide to form new cells

increase glycolytic capacity of muscle fibers (reduces muscle

resistance to fatigue)-> converting a portion of fast oxidative fibers into fast glycolytic fibers:

– decreases in size and number of mitochondria

– Increases in the concentration of glycolytic enzymes

– Increases in fiber diameter (new myofibrils are synthesized)

• Muscle hypertrophy

• Muscle atrophy (teo cơ)

Generation of movements across joints

• Most of skeletal muscles are connected to at least 2 bones by tendons

• When a muscle contracts: one bone moves, the other stays stationary

• A muscle exerts force by contracting, pulling a bone making movement in opposite directions

• Skeletal muscles across joints are arranged in antagonistic groups– The biceps and triceps are antagonistic muscles: each exerts force in a direction that opposes the action of the other: the forearm can be flexed or extended

Cơ nhị đầu (co)

Cơ tam đầu (giãn) Cơ tam đầu (co) Cơ nhị đầu (giãn)

Bone functions

- supporting the body

- allowing motion

- protecting vital organs

- storage system for calcium and phosphorus

- forming blood cells

Structure of bone tissue

Tế bào tạo xương

Khuôn ngoại bào khoáng hóa

Tế bào hủy xương

Fig.21.13 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Bone cells

• Osteoblast ( Tế bào tạo xương): bone forming cells –

“bone maker”

• Osteocyte ( Tế bào xương): mature bone cells

• Osteoclast ( Tế bào hủy xương): bone resorbing cell –”bone breaker”

Osteoblasts and ossification

http://www.sciencephoto.com/media/435812/view

• Osteoblasts produce bone matrix and get

“trapped”/immobilized in the matrix - >

osteocytes trapped in lacunae

and no longer produce new bone tissue

• Osteocytes contact/connect to each other and to nearby osteoblasts by long processes ( canaliculi) : exchange

materials(oxygen, nutrients, wastes…) taken by cells close to blood vessels

http://www.denniskunkel.com/index.php?module=media&pId=102&id=10665

http://faculty.une.edu/com/abell/histo/histolab3.htm

• Giant cells, multinucleated, ruffled border

• Bone resorptive activity:

– acids (HCl) dissolve inorganic compounds (hydroxyapatite) of bone matrix > release Ca, P

– Enzymes break down osteoid (collagens, proteins in bone matrix)

http://faculty.une.edu/com/abell/histo/osteoclast.jpg

http://www.biology-online.org/js/tiny_mce/plugins/imagemanager/files/boa002/AN-nothingF03.jpg

Bone is a dynamic tissue

• Bone tissue can:

– grow during childhood

– heal following a fracture

– changes its structure in response to forces applying on it

– renew its structure

• Bone modeling and bone remodeling

Long bone elongation

– Epiphyseal plate (EP)containing cartilage

– Chrondrocytes in the EP increase in size and number- forming thicker cartilage layer -> wider EP

– Cartilage adjacent to the shaft is replaced by bone-> new bone added to the bone shaft ->

elongated bone length

– When EP is completely filled by bone (late adolescence)->

epiphysial plate closure

• sex hormone (androgens and estrogens) -> plate closure

• When plate closure occurs -> no more bone elongation -> no more increases in height (normally after adolescence )

Sụn tiếp hợp đầu xương

Đầu xương

Fig 21.15 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Bone remodeling

(Qúa trình tái tạo xương)

www.cptc.ctc.edu/library/Bio%20118%20Lecture%

Factors affect bone growth and development

– Sunlight exposure

– fat absorption (vitamin D is fat-soluble)

– Rickets and vitamin D deficiency

hormones: estrogen, testosterone

Structure of smooth muscle, compared with skeletal muscle

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Smooth muscle

• spindle-shaped, uninucleated with a centrally located nucleus

• Thick and thin filaments are obliquely arranged in

various directions

• No sarcomere structure -> not striated (no striation)