Skeletal Muscle

Dr. Josefina Ramos-Franco

Dept. Molecular Biophysics and Physiology
Jelke, rm.1255c
Phone : 2-6433
Email : jrfranco@rush.edu
READING
Boron & Boulpaep Book:

Chapter 9 pages 230-254

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.

Three Types of Muscles

1. skeletal muscle
2. cardiac muscle
3. smooth muscle
. B&L Fig. 17.1

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)

Comparison other Muscle Types

(skeletal vs. cardiac/smooth)
Skeletal Muscle :
1. Voluntary Control
2. Striated Appearance
3. Large, independently operating cells
4. Usually relaxed until needed
(attached to bones, involved in locomotion)
Cardiac Muscle : (only found in heart)
1. Involuntary Control
2. Striated Appearance
3. Cells 100x smaller than in skeletal muscle
4. Neighboring cells operate as unit
(cells electrically & physically coupled)
Smooth Muscle : (wall of hollow organs)
1. Involuntary Control
2. Smooth Appearance (not striated)
3. Small cells
4. Many structure & regulatory variations

Skeletal Muscle
Neuromuscular Transmission

. B&B Fig. 8.4

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)

Morphology & Membrane Organization

of Skeletal Muscle

. B&B Fig. 9.8a

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)

ExcitationContraction (EC) Coupling

RELAXATION

CONTRACTION
1) Membrane
Excitation AP

surface
T-tube

Sarcoplasmic

Ca2+ Reticulum Ca2+

( 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

The Mechanism that Triggers

SR Ca Release

. B&B Fig. 9.9

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

. B&B Fig. 9.4

SLIDING FILAMENT THEORY

Thick Filament Structure

globular head
filamentous tail
Individual
Myosin
Molecules

Thick
Filament

. B&B Fig. 9.4

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 Structure

Individual
Actin
Monomers

Thin
Filament

. B&B Fig. 9.5

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

. B&B Fig. 9.7

Steps in Crossbridge Cycle :

ATP binds and myosin head detaches
ATP hydrolysis energizes the unattached myosin head
Myosin head unattached and energized (cocked)
Energized (cocked) myosin head binds to actin
ADP & Pi are released and power stroke occurs
Thick and thin filament are pulled past each other
Spent myosin head remains attached until ATP binds

Muscle Length-Tension Relationship

Definitions :
1. Isometric = muscle contracts with overall length constant
2. Isotonic = muscle shortens at constant load

. B&B Fig. 9.12

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

Twitch, Summation and Tetanus

Definitions :
1. Twitch = transient contraction elicited by single AP
2. Summation = super-twitch tension elicited by a second
AP occurring before previous twitch ends
3. Tetanus = maximum tension at very high AP frequency
AP = 2 ms long
Twitch = 50-150 ms

. B&B Fig. 9.14

Fast and Slow Twitch Muscle Fibers

Definitions :
1. Fast Twitch = large fibers, fast contraction, fatigue easy
fewer mitochondria, rely on glycolysis
2. Slow Twitch = small fibers, slow contraction, fatigue
resistent, more mitochondria, rely on
oxidative phosphorylation, red color

The Motor Unit

. B&B Fig. 9.15

Motor Unit = motor neuron + all muscle fiber it innervates

1.
2.
3.

Motor units vary in size (3 to 300 muscle fibers)

Motor units are recruited small to large, asynchronously
Fibers in motor unit are either all fast or all slow

Skeletal Muscle Energy Consumption

Lots of ATP needed for,
1) crossbridge cycling
2) SR Ca pumping
3) maintain Na/K gradients (Na-K pumping)
Creatine Phosphate System : rapidly converts ADP to ATP
Oxygen Debt : excess oxygen consumption after vigorous
exercise to replenish creatine phoshpate
ATP levels.

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).