Skeletal muscle hierarchy
Germann & Stanfield, fig 13.1
Muscle → Fascicle → Fibre (cell) → Myofibril → Sarcomere
1
Skeletal muscle fibres
z
Enclosed by sarcolemma
z
Rippled with caveolae at rest (invaginations of sarcolemma)
z
z
Surrounded by basement membrane
z
z
z
z
Allow lengthening without membrane damage
Surround one, sometimes more than one fibre
Loose glycoprotein & collagen network
Provides framework for regeneration
Quadriceps muscle group
z
z
1 million fibres per cross-section
Several million per whole muscle
2
Fibroblasts
z
Reside between fibres
z
z
Perimysium - thick connective tissue layer
z
z
z
z
Secrete thin collagen connective tissue matrix
(endomysium)
Surrounds groups of 10-100 fibres (fascicles)
Contains blood vessels and motor axons
Contains muscle spindles
Epimysium – thick outer connective tissue layer
z
Surrounds whole muscle
3
Germann & Stanfield, fig 13.2
Skeletal muscle structure
4
Jones, Round & Haan, fig 1.11
Skeletal muscle cross-section
Ep – epimysium; P – perimysium; En – endomysium; F - fascicle
5
Skeletal muscle myofibrils
z
Average about 1μm in diameter
100-400 myofilaments per myofibril
z
Myofibrils are separated by:
z
z
z
z
z
Sarcoplasmic reticulum network
Transverse tubules
Mitochondria (sometimes)
Myofibrils per muscle fibre
z
z
As little as 50 in foetal muscle
As many as 2000 in adult muscle
6
The Sarcomere
z
Germann & Stanfield, fig 13.3
Highly organised array of myofibrillar protein filaments
z 2 – 2.5 μm in length (Z-line to Z-line)
z Contractile proteins (actin, myosin)
z Regulatory proteins (troponin, tropomyosin)
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Histology
z
Light Microscope
z Cross striations show A- & I-bands
z Lateral cellular organelles
z Multi-nucleate
z
Electron microscope
z Clear sarcomere structure
z
z
A- & II-bands
H-zone, ZZ-lines, MM-lines
8
Jones, Round & Haan, fig 1.13
Myofilament Arrangement
z
z
100-400 filaments per myofibril
Arrangement
z
z
z
1:6 for myosin (thick)
1:3 for actin (thin)
Skeletal muscle fibre
composition by volume
z
83% myofibrils
z
z
9% sarcoplasmic reticulum
z
z
z
z
z
z
myofilaments
4% terminal cisternae
5% longitudinal tubules
1.5% mitochondria
0.3% t-tubules
NB1: values taken from frog sartorius muscle
NB2: values will vary with species and fibre type
Mobley & Eisenberg. J Gen Physiol 1975;66:31–45.
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Skeletal muscle organelles
z
Transverse tubules (T-tubules)
z
z
z
Invaginations of the cell membrane (sarcolemma)
Penetrate deep into each muscle fibre
Humans
z
z
Amphibians
z
z
z
2 per sarcomere evident at A-I junction
3 per 2 sarcomeres evident at each Z-line
Function to evenly distribute action potentials
Sarcoplasmic reticulum (Ca2+ storage)
z
z
Membrane network surrounding each myofibril
2 connected regions
z
Terminal cisterna (Ca2+ release) into cytosol
z
z
Forms TRIAD with T-tubules at Z-line/I-band region
Longitudinal tubules (Ca2+ uptake)
z
Located around myofibril A-bands
10
Boron & Boulpaep, fig 9-8
Skeletal muscle organelles
11
Muscle
Organelles
Jones, Round & Haan, fig 1.18
12
Skeletal muscle TRIAD
z
Junctional area between:
z Transverse tubules
z
z
Usually appears
flattened at the triad
Sarcoplasmic
reticulum
z
z
z
Electron micrograph
Amphibian skeletal muscle
Terminal cisternae
One portion flanking
a single T-tubule
Site of E-C coupling
z Excitation-Contraction
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Excitation-Contraction Coupling
The process of action potential transduction to
provide an intracellular signal (↑[Ca2+]i) and
subsequent muscle cell contraction
z
z
z
Most commonly focuses on the links between:
z T-tubule action potentials, and
z Sarcoplasmic reticulum Ca2+ release
Mechanism is not entirely understood
Dulhunty (2006). ExcitationExcitation-Contraction coupling from the 1950s into the new millennium. CEPP,
CEPP, 33: 763763-772.
Much is understood about the function of some required components
z Voltage sensor (Dihydropyridine receptor – DHP)
z Ca2+ release mechanism (Ryanodine receptor – RyR)
z Structure, function and operation of the fast link between the two
14
E-C coupling
Berne & Levy, Chapter 12
15
E-C coupling
Jones, Round & Haan, fig 3.4
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E-C Coupling
z
Jones, Round & Haan, fig 3.5
DHP & RyR
z Tetrad proteins
z
4 subunits
Precise alignment in
opposing membranes
Twice as many RyR’s
z Redundant, or
z Provide signal amplification
z
z
z
DHP (T-tubule voltage sensor)
z L-type Ca2+ channel
z Little or no ion flux in
skeletal muscle
z Flux in cardiac muscle: CICR
(Ca2+-Induced Ca2+ Release)
z
RyR (SR Ca2+ release channel)
z Sensitive to ligands
z
z
Caffeine
Ca2+ (CICR)
17