Muscle Contraction

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Classification of the Muscle
 According to the structure: Striated Muscle,
Smooth Muscle

 According to the nerve innervation:

Voluntary Muscle, Involuntary Muscle

 According to the Function: Skeletal Muscle,

Cardiac Contraction, Smooth Muscle
Skeletal Muscle Cardiac Muscle

Smooth Muscle
I. Signal Transmission
Through the
Neuromuscular Junction
Skeletal Muscle Innervation 神经支配
Illustration of the Neuromuscular
Junction (NMJ)
 New Ion Channel Players
 Voltage-gated Ca2+ channel
in presynaptic 突触前 nerve terminal
mediates neurotransmitter release
 Nicotinic Acetylcholine Receptor Channel
in muscle neuromuscular junction (postsynaptic
membrane, or end plate)
Mediates 间接 electrical transmission from
nerve to muscle
 Nerve Terminal Ca2+ channels

Structurally similar to Na+ channels

Functionally similar to Na+ channels
except
Activation 激活 occurs at more positive
potentials
activation and inactivation much slower than
Na+ channels
Neuromuscular Transmission

M
ye
li n
Axon

Axon Terminal

Skeletal Muscle
 Depolarization
Neuromuscular
Nerve action
of terminal Transmission:
channels +
opens Cainvades
potential - - +
Step by Step
axon terminal +
-
- +
- + + -
+ -++
Look - +
here + - -+
 Binding
ACh
ACh
Ca 2+binds
of
is released
ACh
inducesto its
opens
andof
fusion
channel
receptor
diffuses
pore
vesicles onacross
that
thenerve
with is
ACh ACh permeable
postsynaptic
terminal membrane. .
synaptic tocleft.
Na
membrane
+
and K +

Nerve ACh Ca2+

terminal Ca2+
Na+
Na+
Na+
Na+ Na+
K + K +
Na +

K+ K+
ACh Na+ Na+
Na +
K+
Outside

Muscle membrane

Na+ Inside
Na +
K+
K + Na +
K+
K+ K+ K+ K+
Na+ K+ Na+
 End Plate 终板 Potential (EPP)
The movement of Na+ and K+ VNa
depolarizes muscle membrane

Muscle Membrane
0
potential (EPP)
EPP

Voltage (mV)
Threshold
Presynaptic
-90 mV
terminal
VK Time (msec)
Presynaptic
AP
Outside
Muscle membrane
Inside
Voltage-gated
ACh Receptor Channels Inward Rectifier
Na Channels
K Channels
 ACh
Choline
Meanwhile ...
ACh ACh ACh Choline
issohydrolyzed
ACh
Choline unbinds
resynthesized
the channel 水解 by
from
is takencloses
up
Nerve AChE itsinto Choline
receptor
terminal Choline
into ACh
into nerve
and repackaged
terminal
and acetate
into vesicle
ACh
Acetate

ACh
Outside

Muscle membrane

Inside
 Neuromuscular Transmission
 Properties of neuromuscular junction
 1:1 transmission: A chemical transmission which
is designed to assure that every presynaptic
action potential results in a postsynaptic one
 An unidirectional 单向 process
 Has a time delay. 20nm/0.5-1ms
 Is easily affect by drugs and some factors Easily
affected by internal environmental factors

 The NMJ 神经肌肉接头 is a site of considerable

clinical importance
 Anticholinesterase Agents

 Anticholinesterase (anti-ChE) agents inhibit

acetylcholinesterase （乙酰胆碱酯酶）
prolong excitation at the NMJ
Anticholinesterase 抗胆碱酯酶 Agents
1. Normal:
ACh Choline + Acetate
AChE

2. With anti - AchE:

ACh Choline + Acetate

anti - AChE
 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 ))
 NMJ 神经肌肉接头 Diseases
Myasthenia Gravis （重症肌无力）
Autoimmunity to ACh receptor
Fewer functional ACh receptors
Low “safety factor” for NM 神经肌肉
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 神经肌肉
transmission
II. Microstructure of Skeletal
Muscle
 Skeletal Muscle
 40-50% of total body weight
Functions of skeletal muscle
Force production for locomotion 运动 and
breathing
Force production for postural 姿势 support
Heat production during cold stress
 Fascicles 肌束 : bundles 捆 , CT(connective tissue 结缔组织 )
covering on each one
 Muscle fibers: muscle cells
 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)
 Within the sarcoplasm 肌质

Triad （三
联管）

 Transverse 横小管 tubules

 Sarcoplasmic reticulum 肌质网 -Storage sites for calcium
 Terminal cisternae - Storage sites for calcium
Microstructure of Skeletal
Muscle (myofibril 肌原纤维 )
 Sarcomeres 肌小节
 Sarcomere 肌小节 : bundle of alternating
thick and thin filaments
 Sarcomeres join end to end to form myofibrils
肌原纤维

 Thousands per fiber, depending on length of

muscle
 Alternating thick and thin filaments create
appearance of striations 光条纹
 Myosin head is hinged Myosin 肌球蛋白
 Bends and straightens during contraction
 Thick filaments (myosin)
 Bundle of myosin proteins shaped like double-
headed golf clubs
 Myosin heads have two binding sites
Actin binding site forms cross bridge
Nucleotide binding site binds ATP (Myosin ATPase)
 Hydrolysis of ATP provides energy to generate
power stroke
Thin filaments

原肌球蛋白 肌钙蛋白

肌动蛋白
 Thin filaments (actin)
 Backbone: two strands of polymerized globular
actin – fibrous actin
 Each actin has myosin binding site
 Troponin
Binds Ca2+; regulates muscle contraction
 Tropomyosin
Lies in groove of actin helix
Blocks myosin binding
 sites in absence of Ca2+
 Thick filament: Myosin (head and tail)
 Thin filament: Actin, Tropomyosin, Troponin
(calcium binding site)
 III Molecular Mechanism of Muscular
Contraction
 The sliding filament model
 Muscle shortening is due to movement of the actin
filament over the myosin filament
 Reduces the distance between Z-lines
The Sliding Filament Model of Muscle Contraction
Changes in the appearance of a Sarcomere during
the Contraction of a Skeletal Muscle Fiber
 Energy for Muscle Contraction
 ATP is required for muscle contraction
Myosin ATPase breaks down ATP as fiber
contracts
Nerve Activation of Individual
Muscle Cells (cont.)
 Excitation/contraction coupling
 Action potential along T-tubule causes release
of calcium from cisternae 池 of TRIAD

 Cross-bridge cycle
 THE CROSS-BRIDGE CYCLE
Relaxed state

Crossbridge Crossbridge
energised
attachment
A + M ADP Pi

Ca2+ present
A – M ATP AMADPPi

Crossbridge Tension
detachment develops
ADP + Pi
ATP
A M
A, Actin; M, Myosin
Cross Bridge Cycle
 Rigor mortis
 Myosin cannot release actin until a new
ATP molecule binds

 Run out of ATP at death, cross-bridges

never release
Many contractile 收缩性的 cycles occur
asynchronously 变形 during a single
muscle contraction

• Need steady supply of ATP!

 Regulation of Contraction

 Tropomyosin 原肌球
蛋白 blocks myosin
binding in absence
of Ca2+
 Low intracellular
Ca2+ when muscle
is relaxed
 Ca+2 binds to troponin 肌钙蛋白
during contraction
 Troponin-Ca+2
pulls tropomyosin,
unblocking
myosin-binding
sites
 Myosin-actin cross-
bridge cycle can
now occur
 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
 Structures
Structures involved
involved in
in A band I band
EC 兴奋收缩coupling
EC 兴奋收缩 coupling Z disc (myosin) (actin)

 Contractile proteins in striated

条纹 muscle are organised into
sarcomeres 肌小节
 T-tubules and sarcoplasmic
reticulum 肌浆网 are organised
so that Ca release is directed
toward the regulatory (Ca
binding) proteins Z disc M line Z disc

 The association of a t-tubule sarcoplasmic

reticulum
with SR 肌浆网 on either side is
often called a ‘triad’ （三联 t-tubules
管） (tri meaning three) Triad
junctional feet
Structures
Structuresinvolved
involvedin
inEC 兴奋收缩 coupling
EC兴奋收缩 coupling
--Skeletal
SkeletalMuscle
Muscle--
T-tubule
sarcolemma out
in
sarcoplasmic
reticulum

voltage sensor? junction foot

 Ca Controls Contraction
2+

Ca2+ Channels and Pumps

 Release of Ca2+ from the SR 肌浆网
triggers contraction
 Reuptake of Ca2+ into SR relaxes muscle
 So how is calcium released in response
to nerve impulses?
 Answer has come from studies of
antagonist molecules that block Ca2+
channel activity
Dihydropyridine 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, DHP receptor is a voltage-gated
Ca2+ channel
 In skeletal muscle, DHP receptor is
apparently a voltage-sensing protein and
probably undergoes voltage-dependent
conformational changes
 Ryanodine 里阿诺定 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 apparently gates
the ryanodine receptor, opening and closing
Ca2+ channels
 Many details are yet to be elucidated!
 Skeletal
Skeletal muscle
muscle
 The AP:
 moves down the t-tubule
 voltage change detected by
DHP （双氢吡啶） T-tubule
receptors sarcolemma out
in sarcoplasmic
 DHP receptor is reticulum
essentially a voltage-
gated Ca channel
 is communicated to the
ryanodine receptor which
opens to allow Ca out of SR
voltage sensor
 activates contraction (DHP receptor) junctional foot
(ryanodine receptor)
 Cardiac
Cardiac muscle
muscle
 The AP:
 moves down the t-tubule
 voltage change detected by T-tubule
DHP receptors (Ca channels) sarcolemma out
which opens to allow small in sarcoplasmic
amount of (trigger) Ca into the reticulum
fibre
 Ca binds to ryanodine receptors
which open to release a large
amount of (activator) Ca
(CACR)
voltage sensor
& Ca channel junctional foot
 Thus, calcium, not voltage,
appears to trigger Ca release in (DHP receptor) (ryanodine receptor)
Cardiac muscle!
 The
The Answers!
Answers!
Skeletal
 The trigger for SR release
appears to be voltage (Voltage
Activated Calcium 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
Cardiac
 The trigger for SR release
appears to be calcium
(Calcium Activated
Calcium Release - CACR)
 The t-tubule membrane has
a Ca2+ channel (DHP
receptor)
 The ryanodine receptor is
the SR Ca release channel
 The ryanodine receptor is
Ca-gated & Ca release is
proportional to Ca2+ entry
Ca2+ release during Excitation-Contraction coupling

 Action
potential on
motor
endplate
travels
down T
tubules

Ryanodyne R
Ca-release ch.
 Voltage -gated Ca2+ channels open, Ca2+ flows out
SR into cytoplasm
 Ca2+ channels close when action potential ends.
Active transport pumps continually return Ca2+ to SR

Ca ATPase
(SERCA)
 Excitation-Contraction Coupling
 Depolarization of motor end plate (excitation) is
coupled to muscular contraction
 Nerve impulse travels along sarcolemma and down
T-tubules to cause a release of Ca2+ from SR
 Ca2+ binds to troponin and causes position change in
tropomyosin, exposing active sites on actin
 Permits strong binding state between actin and
myosin and contraction occurs
 ATP is hydrolyzed and energy goes to myosin head
which releases from actin
Summary: Excitation-Contraction Coupling
IV Factors that Affect the
Efficiency of Muscle
Contraction
 Tension and Load
 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.
 Preload
Preload is a load on the muscle before
muscle contraction.
Determines the initial length of the
muscle before contraction.
Initial length is the length of the muscle
fiber before its contraction.
It is positively proportional to the
preload.
The Effect of Sarcomere Length on Tension

The Length – Tension Curve

Concept of optimal length
 Types of Contractions I
 Twitch: a brief mechanical contraction
of a single fiber produced by a single
action potential at low frequency
stimulation is known as single twitch.
 Tetanus: It means a summation of
twitches that occurs at high frequency
stimulation
Effects of Repeated Stimulations

Figure 10.15
 Afterload
 Afterload is a load on the muscle after the
beginning of muscle contraction.
 The reverse force that oppose the contractile
force caused by muscle contraction.
 The afterload does not change the initial
length of the muscle,
 But it can prevent muscle from shortening
because a part of force developed by
contraction is used to overcome the
afterload.
 Types of Contractions (II)

 Afterload on muscle is resistance

 Isometric 等容线
 Length of muscle remains constant. Peak tension
produced. Does not involve movement
 Isotonic 等压线
 Length of muscle changes. Tension fairly
constant. Involves movement at joints
 Resistance and speed of contraction inversely
反比 related
Isotonic and Isometric Contractions
Resistance and Speed of Contraction