Human Form & Function 1
NMS Systems
Lecture 10
Somatic Muscle Contraction
Dr. Neil Docherty
My Teaching Objectives
•  To revise the basic hierarchical structure of muscle fibres
down to the level of the sarcomere and the major
myofibrillar proteins
•  To explain the chemistry and mechanics of cross bridge
formation and the sliding filament theory
•  To apply the theories and details of normal muscle
contraction to explain the basis of two pathologies
associated with muscle contraction.
Muscle Fibre Organisation
Muscle Fibre (>100µM diameter, >0.75m length)
Composed of
Myofibrils(1µm diameter whole length of muscle)
Repeating units of
Sarcomeres
Regular arrays of
Thick filaments
(myosin polymer)
18nm diameter
1.6µm length
Thin filaments
(actin polymer)
5-8nm diameter
1µm length
Muscle Fibre Structure
Transmission Electron Microscopy
Regular striated patterns
of filaments and organelles
hint at functionality
The Sarcomere Visualised
A band-stacked thick filaments and
overlapping regions of thin filaments
H-zone-Central thick filament only
Contains M line
I band-Peripheral thin filament only
Terminates at Z line
Area between Z-lines
=SARCOMERE
2.5µm length (resting)
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
The Sarcomere
Order Hints at Function
-T.E.M. patterning reflects
molecular composition
-Mitochondria and sarcoplasmic
reticulum are present
-Think ATP and calcium and purpose of
staggered arrays of myofibrils
Adapted from Human Physiology- Cells to Systems (7th Ed.) Sherwood L
and Wheater’s Functional Histology (5th Ed.) Burkitt H.G. Young B. & Heath J.W.
Sarcomere Geometry
Depending how you look at it!
-Thin filaments form a hexagon around a thick filament
-Thick filaments triangulate a central thin filament
A single thick filament can cross bridge to six thin filaments
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Myosin-The Thick Filament Protein
Several hundred myosin
molecules/thick filament
Mirror Image arrangement
Cross bridging to actin by
globular head
Crucial!
-ATPase site
-Actin binding site
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Actin-The Primary Thin Filament Protein
Spherical polymer of actin monomers
Two polymeric actins intertwine
Each actin monomer contains a myosin binding site
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Troponin/Tropomyosin/Actin Complex
Blocks myosin interaction
TROPONIN
-Ca2+
Stabilisation
of tropomyosin
actin binding
+Ca2+
Destabilisation
of tropomyosin
actin binding
Cross Bridge Formation
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Cross Bridges and Sarcomere Shortening
Multiple cycles of;
1) 
2) 
3) 
4) 
Actin binding
Power stroke
Detachment
Binding
Sarcomere shortened by pulling
in of the Z-lines at each extreme
of the sarcomere
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Band Dimensions During Contraction
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
The Role of ATP
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Calcium Drives The Contractile Apparatus
•  Cross bridge formation requires calcium to bind to
troponin.
-Where is the calcium coming from?
-What is the signal for calcium release?
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Return to the NM Junction
The transfer of the action potential to invaginations in the sarcolemma
is the first step towards elevating intracellular free calcium
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
The Transverse Tubules
AP
Calcium sequestration
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Voltage Depedent Calcium Release Via
The Ryanodine Receptor
SEQUENCE
-Sodium influx
-Voltage dependent activation of
the dihydropyridine receptor
-Activation of caclium release from the ryanodine
receptor
Adapted from Human Physiology Cells to Systems (7th Ed.) Sherwood L.
Muscle Fibres
Uniting Structure and Function
From NM Junction
to Contraction
Summary
-ACh binds nACh
-Na+ influx
-Activation of AP
-Local Spread
-T-tubule depolarisation
-Ryanodine receptor activ.
-Calcium release
-Calcium-troponin bind
-Cross bridges form
-Power stroke/release
-Sarcomere shortening
-Muscle contraction
-Calcium resequestered
-(SERCA)
-Relaxation
Duchenne Muscular Dystrophy (DMD)
Dystrophin involved in stabilising the
contractile apparatus via tethering
between actin and Extracellular matrix.
Mutation cause of X-linked DMD
Fibrotic deterioration of fibres secondary
to calcium leakage in fibre.
Progressive Pathophysiology
Muscle weakness-immobility-respiratory failure
early childhood- pre-pubescent-young adult
Malignant Hyperthermia
• Reflex contraction and heat generation in
skeletal muscle represents a protective
response designed to oppose reductions
in core temperature.
THIS IS HOMEOSTATIC
Massive local release of calcium in
muscle with the onset of generalised
contraction raises body temperature
Above the set-point
THIS IS MALIGNANT
There are myriad consequences
You should have a good idea of what
these are and why they occur by the end
of Human Form and Function
Your Learning from Today
Should focus on being able to
•  Detail the hierarchical structure of muscle tissue
down to the level of the sarcomere.
•  Explain the chemistry and mechanics of excitationcontraction coupling in skeletal muscle.
•  Apply knowledge of skeletal muscle structure and
function to explain the basis of DMD and MH