Transcript Chapter 9 Motor System

Chapter 9 Motor System - 1
Muscle Contraction and Motor Unit
Content
• Skeletal Muscle Contraction
• Motor Unit
Reference – Text Book
P160-163
P56 – 70
P464
P85 – 91
P673 - 674
Section I Skeletal Muscle Contraction
• Signal Transmission Through Neuromuscular
Junction
• Molecular Mechanism of Muscle Contraction
• Factors that Affect the Efficiency of Muscle
Contraction
Part I
Signal Transmission Through the
Neuromuscular Junction
Skeletal Muscle Innervation
9
Illustration of the Neuromuscular
Junction (NMJ)
10
New Ion Channel Players
Voltage-gated Ca2+ channel
in presynaptic nerve terminal
mediates neurotransmitter release
Nicotinic Acetylcholine Receptor Channel
in muscle neuromuscular junction
(postsynaptic membrane, or end plate)
mediates electrical transmission from nerve to
muscle
11
Neuromuscular Transmission
Axon
Axon Terminal
Skeletal Muscle
12
Depolarization
of terminal
Nerve
action
opens Ca channels
potential invades
axon terminal + +
Look
here
+
+
+
Step by Step
-
+
-
+
+
-++
+
-
-
Neuromuscular
Transmission:
-
-
+
13
ACh
Binding
ACh
ACh
binds
ofisACh
released
toopens
its and
Ca2+ induces fusion of
channel
receptor
diffuses
pore
onacross
that
theis
vesicles with +nerve +
permeable
postsynaptic
synaptic
to cleft.
Namembrane
and K .
terminal membrane.
ACh
ACh
Ca2+
Ca2+
Na+
Na+
K+
Na+
K+
Na+
K+
ACh
Na+
Na+
Na+
K+
Na+
Na+
K+
Outside
Muscle membrane
Na+
K+
Na+
Na+
K+
K+
Na+
K+
K+
Inside
K+
K+
K+
Na+
14
End Plate Potential (EPP，终板电位)
Presynaptic
terminal
VNa
Muscle Membrane
Voltage (mV)
The movement of Na+ and K+
depolarizes muscle membrane
potential (EPP)
0
EPP
Threshold
-90 mV
VK
Presynaptic
AP
Time (msec)
Outside
Muscle membrane
Inside
ACh Receptor Channels
Voltage-gated
Na Channels
Inward Rectifier
K Channels
15
ACh
Choline
ACh
ACh
Meanwhile ...
AChresynthesized
is hydrolyzed
by
Choline
Choline
taken
upfrom
ACh
unbinds
soisthe
channel
closes
AChE
into
Choline
intointo
ACh
and
repackaged
nerve
terminal
its receptor
and acetate
Choline into vesicle
ACh
Acetate
ACh
Outside
Muscle membrane
Inside
16
Structural Reality
17
Neuromuscular Transmission
 Properties of neuromuscular junction
 1:1 transmission:
 An unidirectional process
 Has a time delay. 20nm/0.5-1ms
 easily affect by drugs and some factors
 The NMJ is a site of considerable clinical
importance
18
Ach is the natural
agonist at the
neuromuscular
junction.
Related
compounds
Suberyldicholine
is aare
Clinical Chemistry
useful
in the
neuroscience
synthetic
neuromuscular
Carbachol and related
compounds are used
clinically
for GI disorders,
Carbachol
is a
glaucoma,
salivary
synthetic agonist
glandnot
malfunction,
hydrolyzedetc.
by
acetylcholinesterase.
research
agonist.
Tubocurarine
other,
Tubocurarineand
competes
So tubocurarine
is a
related
compounds
with
ACh
for binding
Tubocurarine
is the
neuromuscular
are
used
to paralyze
to
receptorbut does
primary
paralytic
blocking
agent.
muscles
during
surgery.
not
open
the
pore.
ingredient
in curare.
19
Anticholinesterase Agents
Anticholinesterase (anti-ChE 胆碱酯酶抑制剂)
agents inhibit acetylcholinesterase （乙酰胆
碱酯酶）
prolong excitation at the NMJ
20
Anticholinesterase Agents
1. Normal:
ACh
AChE
Choline + Acetate
2. With anti - AchE:
ACh
Choline + Acetate
anti - AChE
21
Uses of anti-ChE agents
Clinical applications (Neostigmine, 新斯的明,
Physostigmine毒扁豆碱)
Insecticides (organophosphate 有机磷酸酯)
Nerve gas (e.g. Sarin 沙林，甲氟膦酸异丙酯。一
种用作神经性毒气的化学剂))
22
NMJ Diseases
Myasthenia Gravis （重症肌无力）
Autoimmunity to ACh receptor
Fewer functional ACh receptors
Low “safety factor” for NM transmission
Lambert-Eaton syndrome（兰伯特-伊顿综
合征 ，癌性肌无力综合征 ）
Autoimmunity directed against Ca2＋
channels
Reduced ACh release
Low “safety factor” for NM transmission
23
Prat II Molecular Mechanism of
Muscle Contraction
Structure of Skeletal Muscle:
Microstructure
Sarcolemma （肌管系统）
Transverse (T) tubule
Longitudinal tubule (Sarcoplasmic reticulum, SR
肌浆网)
Myofibrils （肌原纤维）
Actin 肌动蛋白 (thin filament)
 Troponin （肌钙蛋白）
 Tropomyosin （原肌球蛋白）
Myosin 肌球蛋白 (thick filament)
25
Within the Sarcoplasm
Triad （三联管）
 Transverse tubules （横管）
 Sarcoplasmic reticulum - Storage sites for calcium
 Terminal cisternae - Storage sites for calcium
26
Sarcomeres
 bundle of alternating thick and thin filaments
 join end to end to form myofibrils
 Thousands per fiber, depending on length of
muscle
 Alternating thick and thin filaments create
appearance of striations
27
28
 Thick filament: Myosin (肌球蛋白，head and tail)
 Thin filament: Actin 肌动蛋白, Tropomyosin 原肌
球蛋白, Troponin (肌钙蛋白 calcium binding site)
29
Molecular Mechanism of Muscular Contraction
 The sliding filament model 肌丝滑行
 Muscle shortening is due to movement of the actin
filament over the myosin filament
 Reduces the distance between Z-lines
30
The Sliding Filament Model of Muscle Contraction
31
Changes in the appearance of a Sarcomere during
the Contraction of a Skeletal Muscle Fiber
32
Energy for Muscle Contraction
ATP is required for muscle contraction
Myosin ATPase breaks down ATP as fiber
contracts
33
Nerve Activation of Individual
Muscle Cells (cont.)
34
Excitation/contraction coupling
 Action potential along T-tubule causes release
of calcium from cisternae of TRIAD
 Cross-bridge cycle
35
Begin cycle with myosin already
bound to actin
1. Myosin heads form cross bridges
 Myosin head is
tightly bound to
actin in rigor state
 Nothing bound to
nucleotide binding
site
37
2. ATP binds to myosin
Myosin changes
conformation,
releases actin
38
3. ATP hydrolysis
ATP is broken
down into:
ADP + Pi
(inorganic
phosphate)
Both ADP and Pi
remain bound to
myosin
39
4. Myosin head changes
conformation
 Myosin head
rotates and
binds to new
actin
molecule
 Myosin is in
high energy
configuration
40
5. Power stroke
 Release of Pi from
myosin releases head
from high energy state
 Head pushes on actin
filament and causes
sliding
 Myosin head splits ATP
and bends toward H
zone. This is Power
stroke.
41
6. Release of ADP
 Myosin head is
again tightly
bound to actin
in rigor state
 Ready to repeat
cycle
42
THE CROSS-BRIDGE CYCLE
Relaxed state
Crossbridge
energised
Crossbridge
attachment
A + M l ADP l Pi
Ca2+ present
AlMlADPlPi
A – M l ATP
Crossbridge
detachment
Tension
develops
ADP + Pi
ATP
AlM
A, Actin; M, Myosin
43
Cross Bridge Cycle
44
Rigor mortis
 Myosin cannot release actin until a new ATP
molecule binds
 Run out of ATP at death, cross-bridges never
release
45
Many contractile cycles occur
asynchronously during a single
muscle contraction
• Need steady supply of ATP!
46
Regulation of Contraction
 Tropomyosin blocks
myosin binding in
absence of Ca2+
 Low intracellular
Ca2+ when muscle is
relaxed
47
Ca+2 binds to troponin during
contraction
 Troponin-Ca2+
pulls tropomyosin,
unblocking
myosin-binding
sites
 Myosin-actin
cross-bridge cycle
can now occur
48
How does Ca2+ get into cell?
 Action potential releases intracellular
Ca2+ from sarcoplasmic reticulum (SR)
 SR is modified endoplasmic reticulum
 Membrane contains Ca2+ pumps to actively
transport Ca2+ into SR
 Maintains high Ca2+ in SR, low Ca2+ in
cytoplasm
49
Ca2+ Controls Contraction
Ca2+ Channels and Pumps

Release of Ca2+ from
the SR triggers
contraction

Reuptake of Ca2+ into
SR relaxes muscle
50
Structures involved in EC coupling
- Skeletal Muscle T-tubule
sarcolemma
voltage sensor?
out
in
sarcoplasmic
reticulum
junction foot
Dihydropyridine （DHP, 双氢吡啶）
Receptor
In t-tubules of heart and skeletal muscle
 Nifedipine and other DHP-like molecules bind
to the "DHP receptor" in t-tubules
 In heart,
 a voltage-gated Ca2+ channel
 In skeletal muscle,
 voltage-sensing protein
 undergoes voltage-dependent conformational
changes
52
Ryanodine (利阿诺定 ) Receptor
The "foot structure" in terminal cisternae of SR
 Foot structure is a Ca2+ channel of unusual
design
 Conformation change or Ca2+ -channel activity
of DHP receptor
 gates the ryanodine receptor,
 opening and closing Ca2+ channels
 Many details are yet to be elucidated!
53
Skeletal muscle
 The AP:
 moves down the t-tubule
 voltage change detected
by DHP （双氢吡啶）
receptors
T-tubule
sarcolemma
 DHP receptor is essentially
a voltage-gated Ca channel
out
in sarcoplasmic
reticulum
 is communicated to the
ryanodine receptor
which opens to allow
Ca out of SR
 activates contraction
voltage sensor
(DHP receptor)
junctional foot
(ryanodine receptor)
Cardiac muscle
 The AP:
 moves down the t-tubule
 voltage change detected by DHP
receptors (Ca2+ channels) which
opens to allow small amount of
(trigger) Ca2+ into the fibre
 Ca2+ binds to ryanodine receptors
which open to release a large
amount of (activator) Ca2+
(CACR)
 Thus, calcium, not voltage,
appears to trigger Ca2+ release in
Cardiac muscle!
T-tubule
sarcolemma
voltage sensor
& Ca channel
(DHP receptor)
out
in sarcoplasmic
reticulum
junctional foot
(ryanodine receptor)
Comparison
Skeletal
Cardiac
 The trigger for SR release  The trigger for SR release
appears to be calcium
appears to be voltage
(Calcium Activated Calcium
(Voltage Activated Calcium
Release - CACR)
Release- VACR)
 The t-tubule membrane has
a voltage sensor (DHP
receptor)
 The ryanodine receptor is
the SR Ca release channel
 Ca2+ release is proportional
to membrane voltage
 The t-tubule membrane has a
Ca2+ channel (DHP receptor)
 The ryanodine receptor is the
SR Ca release channel
 The ryanodine receptor is Cagated & Ca release is
proportional to Ca2+ entry
Summary: Excitation-Contraction Coupling
57
Part III Factors that Affect the
Efficiency of Muscle Contraction
Tension 张力 and Load 负荷
 The force exerted on an object by a
contracting muscle is known as tension.
 The force exerted on the muscle by an
object (usually its weight) is termed load.
 According to the time of effect exerted by
the loads on the muscle contraction the load
was divided into two forms, preload and
afterload.
59
Preload 前负荷
Preload
load on the muscle before muscle contraction.
Determines the initial length of the muscle
before contraction.
Initial length
the length of the muscle fiber before its
contraction.
positively proportional to the preload.
60
The Effect of Sarcomere Length on Tension
The Length – Tension Curve
Concept of optimal length
61
Types of Contractions I
 Twitch 单收缩: a brief mechanical
contraction of a single fiber produced
by a single action potential at low
frequency stimulation is known as
single twitch.
 Tetanus 强直收缩: summation of
twitches that occurs at high frequency
stimulation
62
Effects of Repeated Stimulations
Figure63
10.15
1/sec
5/sec
10/sec
50/sec
64
Afterload 后负荷
 Afterload
 load on the muscle after the beginning of
muscle contraction.
 reverse force that oppose the contractile force
caused by muscle contraction.
 does not change the initial length of the
muscle
 prevent muscle from shortening
65
Types of Contractions (II)
 Afterload is resistance
 Isometric 等长
 Length of muscle remains constant. Peak
tension produced. Does not involve
movement
 Isotonic 等张
 Length of muscle changes. Tension fairly
constant. Involves movement at joints
 Resistance and speed of contraction
inversely related
66
Isotonic and Isometric Contractions
67
Resistance and Speed of Contraction
68
69
Muscle Power
Maximal power occurs where the product of
force (P) and velocity (V) is greatest (P=FV)
X
Max Power=
4.5units
70
Section 2. Motor Unit
• a single motor neuron (a motor) and all
(extrafusal) muscle fibers it innervates
• the physiological functional unit in muscle
(not the cell)
All cells in motor unit contract synchronously
Extrafusal Muscle:
innervated by
Alpha motor
neuron
Intrafusal muscle:
innervated by
Gamma motor
neurons
Motor units and innervation ratio
Innervation ratio
Fibers per motor neuron
Extraocular muscle 3:1
Gastrocnemius 2000:1
（腓肠肌）
Purves Fig. 16.4
•The muscle cells of
a motor unit are
not grouped, but
are interspersed
among cells from
other motor units
•The coordinated
movement needs
the activation of
several motors
Overview - organization of
motor systems
Motor Cortex
Brain Stem
Spinal Cord
a-motor
neuron
Final common
pathway
Skeletal muscle
Final common path - a-motor neuron
(-)
(+)
muscle
fibers
Transmitter?
Schwann
cells
motor nerve
fiber
(-)
(+)
axon
hillock
Receptors?
acetylcholine
esterase
NM junction
Final Common Pathway,
a motor pathway consisting of the motor
neurons by which nerve impulses from many
central sources pass to a muscle in the
periphery