Professional Documents
Culture Documents
Syllabus Vol 2 Pt2 SK Handout Final
Syllabus Vol 2 Pt2 SK Handout Final
LEARNING OBJECTIVES
1. Describe 3 types of muscle and give examples of each and their
function.
2. Draw a skeletal muscle sarcomere, label each part and describe
each parts functional significance.
3. Diagram the chemical and mechanical steps in the crossbridge cycle.
4. Draw the thick and thin filament, label each part and describe each
parts functional significance.
5. Describe the process of neuromuscular transmission.
6. Explain the roles of the ryanodine receptor and dihydropyridine
receptor in skeletal muscle excitation-contraction coupling.
7. Describe the phenomena of skeletal muscle twitch, summation and
tetanus.
8. Draw a length tension diagram and explain why the shapes of the
passive and active curves.
9. Describe the differences between fast and slow twitch muscle fibers.
10. Explain the role creatine phosphate in replenishing ATP supplies
and define the term oxygen debt.
Skeletal muscle
cell segment,
note striations
* Huge size
* Multinucleated
EM image of
cell interior
EM image of
cell interior,
intracellular
membranes
stained dark
Skeletal Muscle :
1. Voluntary Control
2. Striated Appearance
3. Large, independently operating cells
4. Usually relaxed until needed
(attached to bones, involved in locomotion)
Skeletal Muscle
Neuromuscular Transmission
Neuromuscular Transmission :
1. Chemical Synapse b/w motor neuron and muscle
2. Neurotransmitter = Acetylcholine (Ach)
3. Receptor = nicotinic AchR (nAchR)
4. nAchR is cation channel, open upon Ach binding
(its opening depolarizes muscle endplate)
Notable Features :
1. Sarcomere = contractile unit, overlapping proteins
2. Transverse tubules (T-tubes) = surface membrane
invaginations continuous with surface
3. Sarcoplasmic Reticulum (SR) = intracellular organelle,
specialized to store and release calcium
4. Triad = junction of one T-tube and two SR elements
(T-SR gap is ~ 100; gap spanned by protein
dense structures called feet)
CONTRACTION
1) Membrane
Excitation AP
surface
T-tube
Sarcoplasmic
( SR )
5) Calcium Uptake
ATP
2) Calcium
Release
2+
Ca
4) Removal of Calcium
Turns-Off Contraction
3) Calcium Activates
Contractile Apparatus
Contractile
Apparatus
ATP
Steps of EC coupling :
1. Surface membrane excitation (AP)
2. T-tube depolarization (by AP) triggers SR Ca release
3. Ca activates contractile apparatus, activates contraction
4. Contractile apparatus active until Ca removed
5. Ca removed by ATP driven SR Ca pump, cell relaxes
Notable Features :
1. DHPR = dihydropyridine receptor, T-tube voltage sensor
2. RyR = Ryanodine receptor, SR Ca release channel, foot
3. DHPR and RyR physically linked together
4. Vm-induced DHPR conformation change conveyed
to RyR causing it to open, releasing Ca from SR
Skeletal SR Ca Release Trigger Mechanism :
Physical functional link between DHPR and RyR
Sarcomere Structure
Thick
Filament
Notable Features :
1. Thick Filament = 300-400 myosin molecules
2. Each myosin has globular head and filamentous tail
3. Myosin tails align side-by-side
4. Globular head extend outward
5. Myosin globular head form crossbridges between
thick and thin filaments
Thin
Filament
Notable Features :
1. Thin Filament = Action + Tropomysin + Troponin
2. Filament core = double-stranded actin helix
3. Tropomysin lies along actin helix groove
4. Troponin attached to end of each tropomysin
5. Troponin had 3 subunits (TN-I, TN-C, TN-T)
Thin Filament Ca Switch :
1. Ca binds to TN-C
2. TN-C conformation change moves tropomyosin
3. Exposes myosin binding sites on actin
Crossbridge Cycle
Notable Features :
1. Passive + Active = Total Tension
2. Passive element due to inherent muscle elasticity
3. Active element due to sarcomere shortening
4. Active length-tension curve is bell-shaped
5. Bell-shape is a consequence of sarcomere structure
Clinical Notes
Malignant Hyperthermia:
An inherited disease manifested by muscle convulsions
resulting in an uncontrollable rise of body
temperature.
One trigger of this syndrome is general anesthetics
(e.g. halothane). Treated by administration of the
muscle relaxant dandrolene.
Disease is linked to a mutation in the skeletal RyR
(making channel hyperactive).
Muscular Dystrophies:
A genetic family of diseases that typically occur in
childhood. Some are manifested by progressive
muscle degeneration and weakness, followed by
loss of heart and lung function.
These diseases are linked to a group of proteins that
form a dystrophin-glycoprotein complex important
in maintaining skeletal muscle structural integrity
(e.g. absence of dystrophin from skeletal muscle
results in Duchenne Muscular Dystrophy).