Lect 02 - Excitable Tissue (Muscle &
Neuron)
MUSCLE PHYSIOLOGY & NEUROPHYSIOLOGY
BIOLOGY (BY2202) PHYSIOLOGY
Prof. Kumlesh K. Dev
Dept. of Physiology, School of Medicine
Trinity College Institute for Neuroscience (TCIN)
Trinity College Dublin
nerve‐to‐muscle communication
the neuron
y
the type
how it signals
the transmitter
the junction
the receptor
the muscle
the type
how it contracts
1
Lect 02 - Excitable Tissue (Muscle &
Neuron)
the muscle
the neuron
the type
y
how it signals
the transmitter
the junction
the receptor
the muscle
the type
how it contracts
types of muscle
Unstriated
muscle
Striated
muscle
Skeletal
muscle
Voluntary
muscle
Cardiac
muscle
Smooth
muscle
Involuntary
muscle
2
Lect 02 - Excitable Tissue (Muscle &
Neuron)
types of muscle
Specialised for contraction to produce force and movement
(n.b. generates heat)
1. Smooth muscle
- weaker, continuous contractions
- cells, central nuclei
2. Cardiac muscle
- strong, continuous contractions
- fibres (branching)
(branching), striations
striations, central nuclei
3. Skeletal muscle
- strong, short contractions
- fibres, striations, peripheral nuclei
smooth muscle
function & feature
– little/weak contractile apparatus
– long, slender, spindle shaped cells
– single central nucleus
– no myofibrils = nonstriated
– composed of
– thick filaments
– thin filaments
located in organs of
– cardiovascular system
– respiratory system
– digestive system
– urinary system
– reproductive system
3
Lect 02 - Excitable Tissue (Muscle &
Neuron)
smooth muscle
innervation
– involuntary (autonomic innervation)
– dual ((stimulatory/inhibitory)
y
y)
– graded, spreading & continuous
contraction
multi-unit
– each cell innervated
– variable force
– e.g. airways, large arteries
single-unit
– few cells directly innervated
– synchronous contraction (myogenic)
– e.g. gut, uterus
types of muscle
Specialised for contraction to produce force and movement
(n.b. generates heat)
1. Smooth muscle
- weaker, continuous contractions
- cells, central nuclei
2. Cardiac muscle
- strong, continuous contractions
- fibres (branching)
(branching), striations
striations, central nuclei
3. Skeletal muscle
- strong, short contractions
- fibres, striations, peripheral nuclei
4
Lect 02 - Excitable Tissue (Muscle &
Neuron)
cardiac muscle
function and feature
– all-or-none (‘twitch’)
– continuous,
ti
rhythmic
h th i
activity
– resistant to fatigue
innervation
– involuntary
– pacemaker
k cells
ll coordinate
di t
contraction of tissue
– electrical conduction
(Purkinje fibres and gap
junctions)
Cardiac muscle
Purkinje
P
ki j fibres
fib
Pale (unstained
glycogen).
Purkinje
fib
fibres
SA Node
AV Node
cardiac muscle
cardiocytes
– are cardiac
di muscle
l cells
ll
– contain myofibrils = striated
– cells contact each other at
intercalated discs
– cells bound together by
- gap junctions
- desmosomes
5
Lect 02 - Excitable Tissue (Muscle &
Neuron)
types of muscle
Specialised for contraction to produce force and movement
(n.b. generates heat)
1. Smooth muscle
- weaker, continuous contractions
- cells, central nuclei
2. Cardiac muscle
- strong, continuous contractions
- fibres (branching)
(branching), striations
striations, central nuclei
3. Skeletal muscle
- strong, short contractions
- fibres, striations, peripheral nuclei
skeletal muscle
composed of
– skeletal muscle tissue
– connective tissue
– nerves
– blood vessels
functions
– movement
– supports viscera
– maintain body temperature
– store nutrients
6
Lect 02 - Excitable Tissue (Muscle &
Neuron)
skeletal muscle
features
– long, unbranched fibres
– many peripheral nuclei
– contractile apparatus
- actin and myosin
- striations
- powerful contraction
– single
i l iinnervation
ti ((one nerve
ending per fibre)
– all-or-none twitch/contraction
muscle‐fibre types (properties)
Type I
Type II
SDH mitochondrial
enzyme activity
high
low
mATPase activity
(anaerobic)
low
high
oxidative capacity
(aerobic) capillaries
high
low
speed of
contraction
slow
fast
resistance to
fatigue
high
low
7
Lect 02 - Excitable Tissue (Muscle &
Neuron)
skeletal muscle: formation
Muscle fibers develop through the fusion of
Myoblast mesodermal cells
skeletal muscle: organisation
─ collagen fibres
(epimysium, perimysium,
endomysium)
d
i ) bl
blend
d tto
form tendon at end muscle
─ tendons attaches skeletal
muscle to bone
─ epimysium surrounds
entire muscle
─ endomysium surrounds
individual muscle fibers
─ perimysuim surrounds
each fascicle
Tendon
8
Lect 02 - Excitable Tissue (Muscle &
Neuron)
bundle of fibers (fascicle)
─ bundle of muscle fibers
(fascicle)
─ composed
d off severall
muscle cells (fibers)
muscle cell/fiber
─ muscle cells make
individual muscle fibers
─ muscle
l fib
fiber cells
ll are llarge
and elongated
─ have multiple peripheral
nuclei
─ produce voluntary
contractions
9
Lect 02 - Excitable Tissue (Muscle &
Neuron)
myofibrils
─ myofibrils composed of
myofilaments
EM of skeletal
muscle
X 26 000
myofilaments (myosin/actin)
─ myofilaments/sarcomeres
composed of
─ thick
thi k fil
filamentt myosin
i
─ thin filaments actin
─ during contraction
sarcomere shortens
─ myosin-binding protein Z line
C binds myosin and
actin
─ striations due to
H zone
shorter
alignment of filaments
of myofibrils
Sarcomere
H zone
I band
A band
Z line
relaxation
I band
shorter
A band
same
width
contraction
ted
Thick filament
Thin filament
Sarcomere shorter
10
Lect 02 - Excitable Tissue (Muscle &
Neuron)
skeletal muscle: summary
transverse and longitudinal tubules Surface membrane of muscle fiber
Myofibrils are
cross-connected
by Transverse
and longitudinal
tubules
Segments of
sarcoplasmic
Reticulum =
Longitudional
(L) tubule
Myofibrils
Lateral
sacs
Transverse (T)
tubule
I band
A band
I band
11
Lect 02 - Excitable Tissue (Muscle &
Neuron)
myosin molecule make thick filaments Actin binding site
• Myosin is composed
of Head and tail
Myosin ATPase site
Heads
• Head contains a
- actin binding site
- myosin ATPase site
• Thick Filament is
composed of Myosin
M l
Molecules
l
Tail
Cross bridge
Myosin molecule
actin molecule make thin filaments Binding site for
attachment with myosin
cross bridge
•Actin
A ti molecules
l
l
form actin helix
Actin molecules
molec les
•Tropomyosin and
Troponin attach to
actin helix
•This forms the
Thin filament
Actin helix
+
(See next slide)
Tropomyosin
Troponin
Thin filament
12
Lect 02 - Excitable Tissue (Muscle &
Neuron)
cross bridge formation
•Thin filaments interact
with Thick filaments
d i
during
excited
i d state
Tropomyosin
Actin
Thin filament
Troponin
Cross-bridge binding sites
•This requires calcium
(stimulated by Ach
receptor activation)
Actin
Troponin
Myosin cross bridge
Relaxed
Cross-bridge binding site
Tropomyosin
Actin binding site
Myosin cross bridge
Excited
•Cross bridge between
- actin
- tropomyosin
- troponin
- myosin
cross bridge formation
Actin molecules in thin myofilament
BINDING Myosin cross
bridge binds to actin
molecule.
Myosin cross bridge
Thin filament ‘slides’
along Thick filament
Z line
POWER STROKE Cross
bridge bends, pulling thin
myofilament inward.
Thin myofilament
Thick myofilament
DETACHMENT Cross bridge
detaches at end of power
stroke and returns to original
conformation.
BINDING Cross bridge binds
to more distal actin molecule;
cycle repeated.
13
Lect 02 - Excitable Tissue (Muscle &
Neuron)
cross bridge cycle
1. Binding of MyosinActin (Ca2+
present)
2. Bending (power
stroke) pulling
myofilament
inward
3. Detachment of
Myosin-Actin and
return to original
confirmation
4. Energised myosin
(ATPase activity)
ready for another
round of binding
Energized
Resting
Binding
Detachment
Bending (power stroke)
Rigor complex
14
Lect 02 - Excitable Tissue (Muscle &
Neuron)
nerve‐to‐muscle communication
the neuron
the type
y
how it signals
the transmitter
the junction
the receptor
the muscle
the type
how it contracts
the neuron
the neuron
y
the type
how it signals
the transmitter
the junction
the receptor
the muscle
the type
how it contracts
15
Lect 02 - Excitable Tissue (Muscle &
Neuron)
nervous system: divisions
THE NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM
(CNS)
PERIPHERAL NERVOUS SYSTEM
(PNS)
SOMATIC NERVOUS SYSTEM
(SNS)
AUTONOMIC NERVOUS SYSTEM
(ANS)
BRAIN
CRANIAL NERVES
SPINAL CORD
SPINAL NERVES
four major brain cells
– brain is a very complex organ
– huge number of specialised cells
– forming a huge number of connections
.
– cell types
Capillaries
form the bloodbrain-barrier (BBB)
Astrocyte
release growth
factors, create
scar tissue, control
BBB
• neurons
Oligodendrocyte
provide Myelin
sheaths that
insulate axons
• astrocytes
• microglia
glial
• oligodendrocytes (CNS)
• schwann Cells (PNS)
Axon
Myelin sheath
Neuron
Microglia
the macrophages of the brain, provide
an immune system against infections
but release molecules that kill neurons
16
Lect 02 - Excitable Tissue (Muscle &
Neuron)
oligodendrocytes
‐ usually make ~10 myelin sheaths each surrounding a different axon ‐ (c.f. Schwann cells in PNS make myelin sheath for one axon only)
‐ each one MYELIN is fatty wrapping which acts as an insulator
‐ axons are myelinated and dendrites are not
‐ myelin increases speed of action potential Myelin
sheath
Node of
Ranvier
microglial
•
•
•
•
•
fixed macrophages found in the brain.
derived from immune system, not neuronal cell lineage
microglia are specialised immune cells
they are phagocytic
activated due to inflammation or injury
Other types of
Fixed Macrophages
11. Dust/Alveolar type (lungs)
2. Histiocytes (connective tissue)
3. Kupffer cells (liver)
4. Microglial cells (nervous)
5. Osteoclasts (bone)
6. Sinusoidal lining cells (spleen)
17
Lect 02 - Excitable Tissue (Muscle &
Neuron)
astrocytes
•
Release & uptake growth
factors
•
Supply nutrients
•
Assist re-uptake of
transmitter
•
Create scar tissue after
brain damage
pericyte
•
•
•
•
•
form part of blood‐brain barrier pericyte is a mesenchymal‐like cell
can differentiate into fibroblast, smooth muscle cell, macrophage associated with walls blood vessels
support function & blood flow regulators in microvasculature
Pericyte
Astrocyte
Basement membrane
blood vessel
l
lumen
Neuron
Endothelial cell
Tight junction
Lymphocyte, Monocyte, Neutrophil
18
Lect 02 - Excitable Tissue (Muscle &
Neuron)
ependymal cells
• Ependyma is a thin epithelial membrane
• lines ventricular system of brain & spinal cord
• Ependyma
d
made of Ependymal
d f
d
l cells, that are ll h
an additional type of neuroglia in CNS
• they line central canal of cord & brain ventricles • are involved in production of CSF
• these cells have cilia
these cells have cilia, which help circulate which help circulate CSF around CNS
• also have microvilli, which absorb CSF
• in ventricles, ependymal cells and capillaries form choroid plexus, which produce CSF
neuronal components
Input Zone
Dendrites
and
Cell body
y
─ 1. soma – cell body
─ 2. dendrites – receive
information
Nucleus
─ 3. axons – conduct
info. away
Conducting Zone
Axon (may be from 1mm
to more than 1m long)
─ 4. synapse – where
two neurons ‘meet’
meet
─ 5. myelin sheath –
protective neuronal
‘covering’
Trigger Zone
Axon hillock
Arrows indicate the
direction in which nerve
signals are conveyed.
Output Zone
Axon terminals
19
Lect 02 - Excitable Tissue (Muscle &
Neuron)
classification: structural one branch
in
out
Unipolar Neuron
─ morphologies
g
differ in shape,
size, processes
─ by number of branches directly
from cell body
in
─ unipolar (1 branch)
out
Bipolar Neuron
─ biopolar (2 branches
b
h )
─ multipolar (many branches)
in
Multipolar Neuron
out
classification: functional
Sensory neurons
─ nerves that make you feel
─ deliver info from sensory
receptors in PNS to CNS
Motor neurons
Communicate
with glands
─ nerves that make you move
─ deliver motor commands
from CNS to PNS, muscle,
glands
Communicate
with muscles
Communicate
with each other
20
Lect 02 - Excitable Tissue (Muscle &
Neuron)
nerve‐to‐muscle communication
the neuron
the type
y
how it signals
the transmitter
the junction
the receptor
the muscle
the type
how it contracts
the junction
the neuron
y
the type
how it signals
the transmitter
the junction
the receptor
the muscle
the type
how it contracts
21
Lect 02 - Excitable Tissue (Muscle &
Neuron)
neurotransmission
1. action potentials reach
presynaptic terminal
2.
2 stimulate Ca2+ entry
3. neurotransmitters
released from synaptic
vesicles
4. neurotransmitter crosses
synaptic junction
(synapse)
5. on postsynaptic terminal
transmitter binds
receptor
6. receptor activated to
transmit a signal in
postsynaptic neuron
at resting potential
At resting potential
22
Lect 02 - Excitable Tissue (Muscle &
Neuron)
threshold reached
Threshold reached
Na+ activation
gate opens
Depolarizing
triggering event
action potential begins
Action potential begins
Na+ activation gate
now fully open
23
Lect 02 - Excitable Tissue (Muscle &
Neuron)
depolarisation (potential reaches 0mV)
Explosive
depolarization;
potential
reaches 0 mV
Na+ activation gate
fully open
K+ activation gate
still closed
peak of action potential (potential reversed)
Peak of
action
potential;
potential
reversed
Na+ inactivation gate
begins to close
K+ gate opens
24
Lect 02 - Excitable Tissue (Muscle &
Neuron)
repolarisation begins
Repolarization
begins
Na+ inactivation gate
closed
K+ gate now open
AP completes (after‐hyperpolarisation starts)
Action
potential
complete;
after
hyperpolarization
begins
Na+ inactivation gate opens;
Na+ activation gate closes
K+ gate still open
25
Lect 02 - Excitable Tissue (Muscle &
Neuron)
after‐hyperpolarisation completes (return to resting potential)
After
hyperpolarization
is complete;
return to
resting
potential
Na+ activation gate
closed
K+ gate closes
summary
Threshold potential
Resting potential
26
Lect 02 - Excitable Tissue (Muscle &
Neuron)
presynaptic transmitter release
─ synaptic vesicles 40-60 nm diameter
─ concentrated in clusters at nerve
terminals
─ neurotransmitter release involves
1. targeting of SVs to release sites
2. docking of SVs to plasma
membrane
3. priming to fuse SVs during impulse
4. fusion/exocytosis & transmitter
release
5. retrieval of SV by endocytosis
─ ‘kiss & run’ process
─ SVs recycle without collapsing into
memb.
Golgi
synaptophysin
Axon
Retrieval
Targeting
Docking/
Priming
Fusion
Exocytosis
(Kiss & Run)
Terminal
postsynaptic receptor activation
1. Neurotransmitters
bind receptors
2 Receptors are then
2.
activated
3. Activation of
Receptors transmits
signal into the cell
4. signals cause the
cell to grow, die,
move, etc…
Many drugs work by binding
receptors
p
Agonist drugs
─ activate receptors like
neurotransmitters
Antagonists drugs
─ inhibit receptors and block
neurotransmitters binding to
receptors
27
Lect 02 - Excitable Tissue (Muscle &
Neuron)
neurotransmitters and receptors
Neurotransmitter
release
action
potential
presynaptic
neuron
action potential
synapse
postsynaptic
neuron
Target cell
responds
what neurotransmitter?
what receptor?
e.g. Acetylcholine
e.g. Cholinergic – Nicotinic & Muscarinic
major neurotransmitters
Major neuroransmitters of the PNS
- Acetylcholine
- Noradrenaline ((Norepinephrine)
p p
)
- Adrenaline (Epinephrine)
Major neurotransmitters of the CNS
- Glutamate
- Gamma-aminobutaric acid (GABA)
Others major neurotransmitters
- Dopamine
- Serotonin (5 HT)
- Histamine
28
Lect 02 - Excitable Tissue (Muscle &
Neuron)
sensory receptors
• Sensory receptors provide sensations of taste,
pressure, pain, touch, temperature, sight, smell,
hearing,
g, body
yp
position
External
Internal
Chemoreceptors
Taste/Smell
O2/C02, pH
Thermo receptors
Skin
Deep in CNS
Osmo receptors
Blood osmolarity
Ph t
Photoreceptors
t
R d &C
Rods
Cones
Nociceptors
nerve ending pain
Mechanoreceptors
Touch / Pressure,
Balance, Motion, Hearing
Muscle length, joint
position, blood pressure
Electroreceptors
Magnetoreceptors
body sensory afferents: to feel
cortex
• Afferents: Body to Brain
• Sensory system is composed
of 3 neurons
3oy
1oy Primary Neuron
Synapse
thalamus
2oy Secondary Neuron
(runs up to thalamus)
Synapse
2oy
3oy Tertiary Neuron
(runs up to cortex)
interpretation occurs in cortex
peripheral nerves
from
body
1oy
29
Lect 02 - Excitable Tissue (Muscle &
Neuron)
body motor efferents: to move
cortex
• Efferents: Brain to Body
• Motor system is composed of
3 neurons
1. Upper Motor Neurons (UMN)
(in cortex)
Synapse
2. Middle Motor Neurons (MMN)
(in spinal cord)
UMN
Synapse
3. Lower Motor Neurons (LMN)
(leave spinal cord)
peripheral nerves
PNS
innervate muscles
to muscles
MMN
LMN
synaptic junctions
nerve-glands
(we won’t
won t cover)
nerve-nerve
(general synapse)
nerve-muscle
(neuromuscular junction)
30
Lect 02 - Excitable Tissue (Muscle &
Neuron)
generalised synapse
Key features
nerve nerve synapse
• nerve-nerve
smaller than a NMJ with
a narrower synaptic cleft
• smooth postsynaptic
membrane gives small
surface area
• may be excitatory or
inhibitory
• numerous transmitter
substances
neuromuscular junction
Key features
• NMJ is larger than a
nerve-nerve synapse with
a wider synaptic cleft
• folds of postsynaptic
membrane gives larger
surface area
Axon of motor
neuron
Myelin
sheath
Axon terminal
Action potential
propagation
in motor neuron
Vesicle of acetylcholine
Acetylcholine
receptor
Action potential
propagation
in muscle fiber
Acetycholinesterase
• the NMJ is always
excitatory
• only one transmitter –
Acetylcholine
Motor
end plate
Contractile elements within muscle fiber
31
Lect 02 - Excitable Tissue (Muscle &
Neuron)
motor end plate potential (MEPP)
• Large, myelinated (alpha)
axons innervate muscles
• Motor end plate is where
Ach binds receptors
• One motor endplate per
muscle fibre
• Spontaneous release of
Ach give a small ‘miniature
end plate potential’ (MEPP)
Action potential
propagation
i muscle
in
l fiber
fib
Motor
end plate
motor end plate
Contractile elements within muscle fiber
motor end plate potential (MEPP)
Miniature End Plate
Potentials (MEPPs)
Membrane Potential (mV)
Muscle
+30
no summation
needed
0
-90
Membrane Potential (mV)
1
2
4
3
Time (ms)
+30
+Curare (ACh
receptor antagonist)
0
Threshold
EPP
-90
1
2
3
4
Time (ms)
32
Lect 02 - Excitable Tissue (Muscle &
Neuron)
motor unit
A Motor unit
• is composed of one motor
neuron and all muscle fibres
it innervates
• all fibres of a motor unit will
contract together providing
stronger force
A large Motor Unit
• may have
h
more > 1000
muscle fibres e.g. biceps
A small Motor Unit
• may have as few as 10
muscle fibres e.g. eye
motor unit
A Motor unit
• one motor neuron can
innervate many
y fibers
• one fiber is only innervated
by one motor neuron
33
Lect 02 - Excitable Tissue (Muscle &
Neuron)
toxins affecting NMJ transmission
Curare
- Blocks Acetylcholine receptors
- Binds irreversibly to receptors
Botulinum toxin
- Blocks acetylcholine release
- Therefore blocks neuromuscular transmission
Black Widow venom
- Excess release of acetylcholine
- Prolonged depolarisation & continuous contraction
Organophosphates (Pesticides & Nerve Gas)
- Blocks acetylcholine-esterase
- Binds irreversibly to acetylcholine-esterase preventing
breakdown of Ach
- Prolonged depolarisation & continuous contraction
comparing synapses
Nerve - Nerve Synapse
Neuromuscular Junction
 nerve-nerve synapse smaller
than
h a NMJ with
i h a narrower
synaptic cleft
 NMJ is larger than a nervenerve synapse with
i h a wider
id
synaptic cleft
 smooth postsynaptic
membrane gives small
surface area
 folds of postsynaptic
membrane gives larger
surface area
 may be excitatory or
inhibitory
 the NMJ is always
excitatory
 numerous transmitter
substances
 only one transmitter –
Acetylcholine
 potential is lower - always
subthreshold
 potential is higher - always
suprathreshold
 summation needed
 no summation needed
34
Lect 02 - Excitable Tissue (Muscle &
Neuron)
NMJ and muscle contraction
1. Neuron innervates
the muscle
2. Releases
acetylcholine
T tubule
Terminal button
Surface membrane of muscle cell
3. Activates Ach
receptors
Acetylcholine
Acetylcholinegated cation
channel
Lateral
sacs of
sarcoplasmic
reticulum
4. Causes increase in
calcium level
5. Results in muscle
contraction via
actin-myosin
interaction
Tropomyosin
Actin
Troponin
Cross-bridge binding
Myosin cross bridge
myasthenia gravis ‐ autoimmune disorder
- body makes antibodies that
attack nicotinic ACh receptors
at NMJ
- smaller End Plate Potential
which may be sub-threshold
- fewer Action potentials in
muscle so muscle contractile
force is reduced
- muscular weakness develops
35
Lect 02 - Excitable Tissue (Muscle &
Neuron)
myasthenia gravis ‐ treatment
- 200–400 cases per million
Symptoms
- eye muscle weakness
- weakness of other limbs
- respiratory muscles – may need
intubation to maintain airway
Treatments
- cholinesterase inhibitors eg
neostigmine
- Immunosuppressants
learning outcomes
To be able to:
1.
–
describe the structure and function of the different types of muscle
Smooth, cardiac, skeletal (type of contraction, innervation etc)
–
comment on their appearance in section
Position and rel. size of nucleus (presence/absence in profile)
–
describe the fibre-types of skeletal muscle
Type I , II, enzymes, properties.
2.
3.
4.
define a motor unit
–
All the muscle fibres supplied by a single neurone
5.
–
describe the structure and function of a neurone
Processes, nuclear form, nucleolus, granules
–
describe myelinated and nonmyelinated nerve axons.
Myelin: wrapping of cell membrane (lipid)
6.
36
Lect 02 - Excitable Tissue (Muscle &
Neuron)
the lab
Radial nerve
Ulnar nerve
Median nerve
//
//
Stimulator 1
Elbow
Stimulator 2
Wrist
NMJ
Muscle
Recorder
D
T1
Distance (D)
T2
Velocity = Time (T1 – T2)
37