Transcript myosin binding site Troponin

Chapter 2-2
THE MUSCLE AND ITS
CONTRACTION

the Neuromuscular Junction (NMJ)
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Skeletal Muscle Innervation
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Illustration of the Neuromuscular
Junction (NMJ)
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New Ion Channel Players
Voltage-gated Ca2+ channel
in presynaptic突触前的 nerve terminal
mediates neurotransmitter release
Nicotinic Acetylcholine乙酰胆碱 Receptor
Channel
in muscle neuromuscular junction (postsynaptic
突触后的 membrane, or end plate)
mediates electrical transmission from nerve to
muscle
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Nerve Terminal
2+
Ca
channels
Structurally similar to Na+ channels
Functionally similar to Na+ channels
except
activation occurs at more positive potentials
activation and inactivation much slower than
Na+ channels
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Neuromuscular Transmission
Axon
Axon Terminal
Skeletal Muscle
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Depolarization去极化
of terminal
opens Ca channels + +
Nerve action
potential invades- +
axon terminal + -
-
Neuromuscular
Transmission:
+
Step by Step
-
+
+
-
++
Look - +
here + -
-+
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Ca2+ induces fusion熔合
of vesicles with nerve
terminal membrane.
ACh is released and
Diffuses扩散 across
synaptic cleft. ACh ACh
ACh
Ca2+
Binding of ACh opens
channel pore that is
permeable to Na+ and K+.
Ca2+
Na+
Na+
Na+
K+
Na+
K+
Na+
K+
Na+
Na+
ACh
K+
Na+
Na+
K+
Outside
Muscle membrane
ACh binds to its
K+
receptor
on the
K+
K+
postsynaptic membrane
Na+
Na+
Na+
Inside
K+
Na+
K+
K+
K+
K+
Na+
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End Plate Potential (EPP)
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
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K Channels
Structural Reality
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Neuromuscular Transmission
 Properties特性 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单向性 process
 Has a time delay. 20nm/0.5-1ms
 Is easily affect by drugs and some factors
 The NMJ is a site of considerable clinical
importance
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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
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Microstructure of Skeletal
Muscle
Skeletal Muscle
Human body contains over 400 skeletal
muscles
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
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 Fascicles肌束: bundles, CT(connective tissue结缔组织
) covering on each one
 Muscle fibers: muscle cells
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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)
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Within the sarcoplasm
Triad （三
联管）
 Transverse tubules
 Sarcoplasmic reticulum -Storage sites for calcium
 Terminal cisternae - Storage sites for calcium
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Microstructure of Skeletal
Muscle (myofibril)
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Sarcomeres
 Sarcomere 肌小节: bundle of alternating
thick and thin filaments
 Sarcomeres join end to end to form myofibrils
 Thousands per fiber, depending on length of
muscle
 Alternating thick and thin filaments create
appearance of striations条痕
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Myosin 肌球蛋白
Myosin head is hinged铰链
Bends and straightens during contraction
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Thick filaments (myosin)
Bundle of myosin proteins shaped like doubleheaded golf clubs
Myosin heads have two binding sites
Actin binding site forms cross bridge
Nucleotide核苷酸 binding site binds ATP (Myosin
ATPase)
Hydrolysis水解 of ATP provides energy to generate
power stroke
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Thin filaments
原肌球蛋白
肌钙蛋白
肌动蛋白
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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+
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 Thick filament: Myosin (head and tail)
 Thin filament: Actin, Tropomyosin, Troponin
(calcium binding site)
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