Skeletal Muscle

Outline
Structure
Molecular mechanism of contraction
Molecular characteristics of contractile
proteins
Interaction between myosin and actin on
muscle contraction
Neuromuscular junction

Skeletal muscle
Skeletal muscle makes up 40 % of body mass
Smooth muscle, cardiac muscle, make up 5-10 % of
body mass

Skeletal muscle- voluntary contraction, striated, multinucleate, terminal cell type

Smooth muscle-involuntary contraction, non-striated,
uninucleate, can undergo mitosis
Cardiac muscle, involuntary contraction, striated, uni- or
binucleate nuclei, slow dividing, terminal cell type

Nomenclature
Sarcolemma- plasma membrane
Sarcoplasmic reticulum- endoplasmic
reticulum
Muscle fiber- cell
Myofibril-subcellular fibers
Sarcomere - functional unit of myofibril

Muscle zones

A band = thick and thin filaments

I band = thin filaments only
Z line = actin attachment point
H band = thick filaments only

Molecular Mechanism of
Contraction
Sliding filament theory of contraction
Shortening of the sarcomere is caused by
increased overlap between thick and thin
filaments, not shortening of thick and thin
filaments

Sliding Filament Theory of Muscle Contraction

Optimal overlap between thick and thin filaments

Molecular Characteristics
of Contractile Filaments
Myosin (thick filament)

actin binding domain

ATPase site
ATP binding
molecular hinges

Myosin:
Actin binding site
ATP/ADP binding
sites
ATPase site

Actin (thin) filament

Polymerized chain of G actin - called
filamentous actin (F actin). Double helix
tropomyosin- wraps around actin,
covers myosin binding domain
troponin- 3 subunits attached at periodic
locations along tropomyosin fiber
tropomysin binding domain
calcium binding domain

Interaction Between Actin and

Myosin to Cause Contraction
Pure actin and myosin will bind to each other readily
If troponin-tropomyosin complex added, inhibits actin
and myosin binding, therefore active binding sites on
actin filament are blocked by troponin-tropomyosin
complex
When calcium ions bind to troponin, active binding sites
are uncovered and conformational change allows myosin
to bind to actin
As sites become uncovered, myosin binds to actin

Cross-bridges on either side of the thick filament face each other.

isometric
isotonic

Excitation-contraction
coupling
All muscle tissue is irritable,ie.,
depolarizes when electrically stimulated
Nicotinic cholinergic receptors on the
sarcolemma are ligand-regulated Na+
channels
Therefore, when Ach binds, Na+ enters
and muscle depolarizes
The motor nerves innervating skeletal
muscle originate in the ventral horn of the
spinal cord (somatic motor NS) and are
cholinergic

Motor unit=motor nerve and fibers that it innervates. One motor

nerve may innervate 100 muscle fibers, but each muscle fiber is
innervated by only one nerve

End plate potential

T-tubules
Application of small amounts of electrical current around
Z line, but not other areas, is capable of producing a
contraction
Anatomical studies in frog muscle indicated a series of
sarcolemma invaginations that carry current to inner
myofibrils- T-tubules
Each T-tubule bordered on either side by swollen region
of sarcoplasmic reticulum, lateral or terminal cisterna(e);
together this structure is called a triad
Cardiac muscle similar, 1 T-tubule and 1 lateral cisterna
= Diad

AP causes Ca2+
channels in SER to open

Neuromuscular junction
Specialized synapses between cholinergic motor
neurons and skeletal muscle
Each motor neuron may innervate 1-100
individual muscle fibers
Each muscle fiber innervated by only one motor
neuron
1 motor neuron and all muscle fibers it
innervates is called a motor unit
Acetylcholinesterase- enzyme in the cleft that
degrades acetylcholine

Recruitment of Motor Units

Each muscle fiber contracts in an all-ornothing fashion
If so, then how do whole muscles
contract in a graded or proportional
fashion?
Answer: Differential recruitment of motor
units.

Clinical Correlations
Drugs that interfere with neuromuscular junction
nicotine- binds irreversibly to nicotinic receptors
Acetylcholinesterase inhibitors- neostigmine,
prolonged muscle contraction
Curare- poison dart frog skin, blocks Ach
receptors, muscle relaxation
Strychnine- inhibits glycine input to motor neurons in
spinal cord. Normally, glycine inhibits motor neurons.
Strychnine causes disinhibition of motor neurons,
over-activation of motor neurons and convulsions

Clinical Correlations
(cont)
Amyotrophic lateral sclerosis (ALS)- Also known
as Lou Gehrigs disease. Scar tissue forms
around motor neurons causing death of motor
neurons and muscle weakness. 90% of cases
have no cause
Myasthenia gravis- autoimmune disease that
attacks muscle nicotinic receptors

ATP conservation
If muscle is stimulated, ATP levels dont
change
Creatine phosphate is a muscle storage
form of phosphate

Cardiac muscle