Download Chapter 9 Muscle

Chapter 9

Skeletal muscle 骨骼肌

Smooth muscle 平滑肌
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Introduction

Three types of muscle tissue can be identified on the basis of structure
基本結構, contractile properties 收縮特性, and control mechanisms 控制
機轉—skeletal muscle 骨骼肌, smooth muscle 平滑肌, and cardiac
muscle 心肌

Most skeletal muscle is attached to bone, and its contraction is
responsible for supporting and moving the skeleton 骨骼  is usually
under voluntary control 隨意識控制

Sheets of smooth muscle surround various hollow organs and tube,
including the stomach 胃, intestine 腸, urinary bladder 膀胱, uterus 子宮,
blood vessels 血管, and airways 呼吸道 in the lungs  is not normally
under voluntary control 不隨意識控制

Cardiac muscle is the muscle to the heart  like smooth muscle, it is
regulated by the autonomic nervous system 自律神經系統, hormones,
and autocrine/paracrine agents 自泌素/旁泌素, and it can undergo
spontaneous 自發性的 contractions
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Skeletal muscle

Skeletal muscle  a distinct series of alternating light and dark
bands perpendicular to the long axis 明帶暗帶交替的橫紋垂直於橫軸

Cardiac muscle shares this characteristic striped pattern  skeletal
& cardiac muscles are both referred to as striated muscle 橫紋肌

Smooth muscle  it lacks this striated appearance 缺乏橫紋
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Structure

A single skeletal muscle cell is know as a muscle fiber 肌肉纖維
 lengths that may extend up to 20 cm  is form during
development by the fusion of a number undifferentiated 未分化的,
mononucleated 單核的 cells, known as myoblasts 肌母細胞

If skeletal muscle fibers are destroyed 破壞的 after birth as a result of
injury, they cannot be replaced by the division 分裂 of other existing
muscle fibers 已存在的肌肉細胞不具有增生複製的能力

New fibers can be formed, from undifferentiated cells known as
satellite cells 衛星細胞, which are located adjacent 附近 to the
muscle fibers  the new skeletal muscle fibers is considerable
相當多 but will not restore a severely damaged muscle to full
strength 雖然新增生的肌肉纖維很多，但仍不足以恢復完全的強度
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Structure

The term muscle refers to a number of muscle fibers bound together
by connective tissue 許多肌肉纖維以結締組織束在一起稱為肌肉

Muscles are usually linked to bones by bundles of collagen fibers
known as tendons 肌腱
許多的膠原纖維束在一起稱為肌腱，大多數的肌肉則是藉由肌腱與骨骼
連接在一起
Figure 9-2
p280-281
Structure

The striated pattern 橫紋 in skeletal muscle
results from the arrangement of numerous
thick 粗的 and thin filaments 細肌絲 in
cytoplasm into myofibrils 肌原纖維

One unit of this repeating pattern 重複的趨勢
is known as a sarcomere 肌小節

The thick filaments are
composed almost entirely of the
contain the contractile protein
myosin 肌凝蛋白

The thin filaments contain the
contractile 可收縮的 protein
actin 肌動蛋白, as well as two
other proteins—troponin 旋轉素
and tropomyosin 旋轉肌凝素
Figure 9-2
p280-281
Structure

The thick filaments are located in middle of each sarcomere, where their
orderly parallel arrangement produced a wide, dark band known as the A
band 粗肌絲位於每個肌小節的中間，平行排列成一個寬的暗帶，稱為A 帶

Each sarcomere contain two sets of thin filaments, one at each end 
one end of each is anchored to a network of interconnecting protein
known as the Z line 每個肌小節含有兩組細肌絲，每一組的一端固定在彼此
互相連接在一起的蛋白Z線上

A light band known as the
I band, lies between the
ends of the A bands of two
adjacent sarcomeres and
contains those portions of
the thin filaments that do
not overlap the thick
filaments 亮帶又稱為I帶，
位於兩個相鄰的肌小節之間，
是由細肌絲跟粗肌絲沒有重
疊的部份所組成
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Structure

Two additional bands are present in the A band region of each
sarcomere  the H zone 區 & M line

Thick filaments composed of the elastic protein 彈性蛋白 titin 微絲
extend from the Z line to the M line and are linked to both the M line
protein and the thick filaments 粗肌絲上含有一種彈性蛋白，稱為微絲，
將粗肌絲從Z線延伸到M線相連在一起
Figure 9-3
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Structure

A cross section 橫切面 through the A bands shown the regular
arrangement of overlapping thick and thin filaments
Figure 9-4
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Muscle
Muscle cells
Myofibrils
Sarcomeres
Thick + thin filaments
Myosins (+titin) + actins (+troponin+tropomysin)
Molecular mechanisms of contraction

The term contraction 收縮 does not necessarily mean “shortening” 縮短
 it simply refers at activation 活化 of the force-generating sites 力量
產生的作用點 within muscle fibers—the cross-bridges 橫橋

Following contraction, the mechanisms that generate force are turned
off 關閉, and tension declines 張力下降, allowing relaxation 鬆弛 of the
muscle fiber
Sliding-filament mechanism

When force generation produces shortening of a skeletal muscle fiber,
the overlapping thick and thin filaments in each sarcomere move past
each other, propelled 推動 by the movements of the cross-bridges

During this shortening of the sarcomere, there is no change in the
lengths of either the thick or thin filaments  this is known as slidingfilament mechanism 肌絲滑動機轉
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Sliding-filament mechanism
Figure 9-6
Figure 9-5
p283-284
Sliding-filament mechanism

An actin 肌動蛋白 molecule is a globular protein 球形蛋白 composed
of a single polypeptide 單一胜肽鏈 that polymerizes 聚合 with other
actins to form two intertwined helical chains 互相纏繞的雙股螺旋

This chains make up the core 核心 of a thin filament  each actin
molecule contain a binding site 結合位 for myosin
Figure 9-7
Thin filament = actin polymers +
tropomyosin + troponin
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Role of troponin, tropomyosin,
and calcium in contraction

Tropomyosin 旋轉肌凝素 is a rod-shaped 桿狀 molecule composed of two
intertwined polypeptides 雙股螺旋胜肽 with a length approximately equal
to that of seven actin molecules 與7個actin的長度相等

These tropomyosin molecules partially cover the myosin-binding site
on each actin molecule 部分覆蓋住每個肌動蛋白上的肌凝蛋白結合位,
thereby preventing the cross-bridges from making contain with actin
防止橫橋與actin結合

Troponin 旋轉素 is composed of three subunits 三個次單位 designated by
the letters I (inhibitory), T (tropomyosin-binding), and C (calcium
binding)
Figure 9-9
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Sliding-filament mechanism

The myosin 肌凝蛋白 molecule is composed of two large polypeptide heavy
chains 重鏈 and four smaller light chains 輕鏈

This polypeptides combine to form a molecule that consists of two globular
heads (containing heavy and light chains) and a long tail formed by the
two intertwined heavy chain

The tail of each myosin molecule lies along the axis of the thick filament,
and the two globular heads extend out to the sides, forming the crossbridges 橫橋  each globular head contains two binding sites, one for
actin and one for ATP

The ATP binding site also serves as an enzyme—an ATPase that
hydrolyzes the bound ATP, harnessing 產生動力 its energy for contraction
Figure 9-7
p284

The sequence of events that
occurs between the time a
cross-bridge binds to a thin
filament, moves, and then is
set to repeat the processes
is known as a cross-bridge
cycle 橫橋週期
鈣離子濃度增加
結合troponin
使tropomysin移動
暴露出myosin結合位
橫橋與肌動蛋白結合
橫橋產生移動
ADP及Pi釋出
ATP結合到myosin上
造成橫橋與actin解離
ATP水解，釋出能量給予myosin
Figure 9-8
p284-286
Sliding-filament mechanism

The importance of ATP in dissociating actin and myosin
during step 3 of a cross-bridge cycle is illustrated by
rigor mortis 屍僵, the stiffening 僵硬 of skeletal
muscles that begins several hours after death and is
complete after about 12 hour

In the absence of ATP, the breakage of the link between
actin and myosin does not occur
在死亡後，因缺乏ATP，故myosin無法從actin上解離開，
而造成骨骼肌僵硬的現象

Figure 9-8
The stiffness of rigor mortis
disappears 消失 about 48 to 60
hour after death as the muscle
tissue disintegrates 崩解
p285-286
Role of troponin, tropomyosin,
and calcium in contraction

Tropomyosin 旋轉肌凝素 is a rod-shaped 桿狀 molecule composed of two
intertwined polypeptides 雙股螺旋胜肽 with a length approximately equal
to that of seven actin molecules 與7個actin的長度相等

These tropomyosin molecules partially cover the myosin-binding site
on each actin molecule 部分覆蓋住每個肌動蛋白上的肌凝蛋白結合位,
thereby preventing the cross-bridges from making contain with actin
防止橫橋與actin結合

Troponin 旋轉素 is composed of three subunits 三個次單位 designated by
the letters I (inhibitory), T (tropomyosin-binding), and C (calcium
binding)
Figure 9-9
p286-287
Role of troponin, tropomyosin,
and calcium in contraction

When calcium 鈣離子 binds to specific binding sites on the calciumbinding subunit of troponin  produces a change in the shape of
troponin  drags 拖拉 tropomyosin away from 離開 the myosinbinding site on each actin molecule

Thus, cytosolic calcium ion concentration determines the number of
troponin sites occupies by calcium, which in turn determines the
number of actin sites available for cross-bridge binding
因此，細胞質內鈣離子濃度多寡可決定troponin被鈣離子結合的數目，進而
決定有多少的actin暴露出橫橋結合位，而決定收縮的強度
Figure 9-9
p286-287
Excitation-contraction coupling

Excitation-contraction coupling 興奮-收縮偶合 refers to the sequence of
events by which an action potential in the plasma membrane of a muscle
fiber leads to cross-bridge activity 骨骼肌細胞產生動作電位到橫橋移動、
肌肉收縮的一連串過程稱之

The skeletal muscle plasma membrane is an excitable membrane
capable of generating and propagating action potential

The electrical activity in the plasma membrane does not directly act upon
the contractile proteins, but instead produces a state of increased
cytosolic calcium concentrations 動作電位並不直接影響收縮性蛋白，
而是增加細胞內鈣離子濃度

In a resting muscle fiber, the concentration of free, ionized calcium in the
cytosol surrounding the thick and thin filaments is very low, only about
10-7 mol/L 在休息狀態，細胞質內鈣離子濃度非常低

The source of the increased cytosolic calcium is the sarcoplasmic
reticulum 漿質網 within the muscle fiber 細胞內的鈣離子 主要存在漿質網
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Sarcoplasmic reticulum

The sarcoplasmic reticulum
(SR) 漿質網 in muscle is
homologous 同源的 to the
endoplasmic reticulum (ER)
內質網 found in most cells

SR forms a series of sleeve-like
segments around each myofibril
一系列像袖子衣樣的分節環繞在
每個肌原纖維外面  at the end
of each segment are two
enlarged regions, known as
lateral sacs 側囊

A separate tubular structure, the
transverse tubule 橫小管 (Ttubule), lies directly between
the lateral sacs of adjacent
segments of the SR
Figure 9-11
p287-288
Sarcoplasmic reticulum

The membrane of the T-tubule is able to propagate action potential
能夠傳導動作電位  once initiated in the plasma membrane, an action
potential is rapidly conducted over the surface of the fiber and into its
interior by way of the T-tubules 經由橫小管將 動作電位傳入細胞內

The T-tubules are in intimate contact 親密的接觸 with the lateral sacs of
the SR, connected by structures known as junctional feet 連接足 or “foot
proteins” 足蛋白

This junction involves two integral membrane proteins  dihyropyridine
(DHP) receptor & ryanodine receptor
位於SR的側囊上，
為一種鈣離子通道
位於橫小管上，
因動作電位而開啟 因DHP活化而開啟
Figure 9-12
p287-289
Sarcoplasmic reticulum

Calcium is thus released from
the lateral sacs of the SR into
the cytosol, activating crossbridge cycling

The membranes of the SR
contain primary active transport
proteins 主動運送蛋白—Ca2+ATPase—that pump calcium
ions from the cytosol back into
the lumen of the SR

ATP is required to provided to
provide the energy for the
calcium pump
Figure 9-12
p289-290
Membrane excitation:
the neuromuscular junction

The nerve cells whose axons innervate skeletal muscle fibers are known
as motor neurons (or somatic efferent neurons) 體運動神經, and their
cell bodies are located in either the brainstem or the spinal cord

Upon reaching a muscle, the axon of a motor neuron divides into many
branches, each branch forming a single junction with a muscle fiber

A motor neuron plus the muscle fibers it innervates is called a motor
unit 運動單位  the muscle fibers 肌肉纖維 in a single motor unit are
located in one muscle 肌肉, but they are scattered 分散 throughout the
muscle and are not adjacent 不相鄰 to each other
Figure 9-13
p290
The neuromuscular junction

The region of the muscle fiber plasma membrane that lies directly
under the terminal portion of the axon 軸突末梢 is known as the motor
end plate 運動終板

The junction 聯合 of an axon terminal 軸突末梢 with motor end plate
運動終板 is known as a neuromuscular junction 神經肌肉聯合
Figure 9-14
p290-291
The neuromuscular junction
Figure 9-15
p291
The neuromuscular junction

ACh diffuses from the axon terminal to the motor end plate where it
binds to receptors (of the nicotinic type)

The binding of ACh opens an ion channel in each receptor protein 
both sodium (Na+) and potassium ions (K+) can pass through channels

Because of the differences in
electrochemical gradients 電化學梯
度差 across the plasma membrane,
more Na+ moves in than the K+ out,
producing a local depolarization
局部去極化 of the motor end plate
know as an end-plate potential (EPP)
終板電位

An EPP is an analogous 類似 to an
EPSP at a neuron-neuron synapse
p292
The neuromuscular junction

The magnitude of a single EPP is much larger than that of an EPSP
because ACh is released over a larger surface area, binding to many
more receptors and opening many more ion channels

This is quite different from synaptic junctions between neurons,
where multiple EPSPs must occur in order for threshold to be
reached and an action potential elicited in the postsynaptic
membrane

A second difference between inter-neuronal synapses and
neuromuscular junctions is notable  inhibitory potentials (IPSPs)
do not occur in human skeletal muscle & all neuromuscular
junctions are excitatory 所有的神經肌肉聯合都是興奮性的
p292
p293
Disruption of neuromuscular signaling

The deadly South American arrowhead poison curare 南美箭毒 binds
strongly to nicotinic Ach receptors, but it does not open their ion
channels and acetylcholinesterase does not destroy 破壞 it

Therefore, although the motor nerves still conduct normal action
potentials and release Ach, there is no resulting EPP and contraction
 can cause death by asphyxiation 窒息

Some organophosphates 有機磷酸鹽類, which are the main ingredients
in certain pesticides 殺蟲劑 and nerve gases 神經毒氣  inhibit
acetylcholinesterase  Ach   a maintained EPP  cannot
generate action potentials because the voltage-gated Na+ channel
become inactivate, which requires repolarization to reverse

Thus, the muscle does not contract in response to subsequent nerve
stimulation, and the result is skeletal muscle paralysis 骨骼肌麻痺 and
death from asphyxiation 窒息

Botulinum toxin肉毒桿菌毒素 (botulism 肉毒桿菌病) is an enzyme that
breaks down a protein required for the binding and fusion of Ach vesicles
with the plasma membrane of the axon terminal  Ach 
p292-293
Mechanisms of single-fiber contraction

The force exerted on an object by a contracting muscle 肌肉收縮作用
在物體上的力量 is known as muscle tension 肌肉張力, and the force
exerted on the muscle by an object (usually its weight) 物體作用在肌肉
上的力量 is the load 負重  tension & load are opposing 相反方向

When a muscle develops tensions but does not shorten (or lengthen),
the contraction is said to be isometric (constant length) 等長收縮

A contraction in which the muscle shortens, while the load on the
muscle remains constant, is isotonic (constant tension) 等張收縮

A lengthening contraction 伸長收縮 occurs when an unsupported
load on a muscle is greater than the tension the cross-bridges are
generating

The mechanical response of a single muscle fiber to a single action
potential is known as a twitch 單次收縮；抽動
p294
Figure 9-16
p295
Skeletal muscle energy metabolism

ATP performs three functions directly related to muscle fiber
contraction and relaxation  the small supply of performed ATP that
exists at the start of contractile activity would only support a few twitches
在肌肉收縮鬆弛時，ATP執行三個功能，但細胞內只有少量現成的ATP
供應，因此只夠完成幾次肌肉收縮

There are three ways a muscle fiber can form ATP: (1) phosphorylation
磷酸化 of ADP by creatine phosphate 磷酸肌胺酸, (2) oxidative
phosphorylation 氧化磷酸化 of ADP in the mitochondria 粒線體, and
(3) phosphorylation of ADP by the glycolytic 醣解的 pathways in the
cytosol 細胞質

During periods of rest, muscle fibers build up a concentration of creatine
phosphate approximately 5 times 倍 that of ATP
p298-299
休息狀態時，磷酸肌胺酸是ATP的5倍量

If contractile activity is to continue for more than a few seconds, the
muscle must be able to form ATP from the other two sources
若收縮持續幾秒鐘以上，磷酸肌胺酸用完，ATP就必須從其他兩種來源來
Figure 9-22
p299
Skeletal muscle energy metabolism

At moderate levels 中等程度的 of muscular activity, most of the ATP used
for muscle contraction is formed by oxidative phosphorylation

During the first 5~10 min of such exercise, breakdown of muscle
glycogen to glucose provides the major fuel contributing to oxidative
phosphorylation 在最初的5-10分鐘，在粒線體進行氧化磷酸化產生ATP
的主要來源為肌肉細胞內儲存的肝糖所分解出的葡萄糖

For the next 30 min or so, blood-borne fuels become dominant, blood
glucose and fatty acids contributing approximately equally
在接下來的30分鐘內，血液所提供的葡萄糖及脂肪酸同等重要

Beyond this period, fatty acids become progressively more important,
and the muscle’s glucose utilization decrease 之後，脂肪酸漸漸變的越來
越重要，而葡萄糖的利用漸漸減少

If the intensity of exercise exceeds about 70% of the maximal rate of ATP
breakdown, however, glycolysis contributes an increasingly significant
fraction of the total ATP generated by the muscle 假如運動程度超過ATP
分解速率的70%以上，此時藉由醣解作用產生ATP的比率逐漸增加
p299
Skeletal muscle energy metabolism

The glycolytic pathway  produce only small quantities of ATP from
each molecule of glucose metabolized, and it can do so in the absence
of oxygen (O2)  produce lactic acid 每分子的葡萄糖經糖解作用只能
產生少量的ATP，但可在無氧下進行，其副產物為乳酸

At the end of muscle activity, creatine phosphate and glycogen levels
in the muscle have decreased 運動後，磷酸肌胺酸及肝醣的濃度都降低

Extra O2 is required to metabolize accumulated lactic acid and return
the blood and interstitial fluid O2 concentrations to pre-exercise values
運動後，需要額外的氧氣來代謝累積的乳酸，並且要使血液及間質液中的
氧氣恢復到運動前的濃度

This elevated O2 consumption following exercise repays 償還 the
oxygen debt 氧債—that is, the increased production of ATP by oxidative
phosphorylation following exercise is used to restore the energy
reserves in the form of creatine phosphate and glycogen
在運動過後，氧氣的消耗量增加，稱為氧債，除了代謝乳酸、恢復血氧濃度
外，也為了恢復細胞內磷酸肌胺酸及肝醣的儲存
p299
Types of skeletal muscles fibers

Different types of fibers can be identified on the basis of (1) their maximal
velocities of shortening—fast or slow—and (2) the major pathway they
use to form ATP—oxidative or glycolytic

Fibers containing myosin with high ATPase activity are classified as fast
fiber 快肌  with lower ATPase activity are called slow fibers 慢肌

Some fibers contain numerous mitochondria 含很多粒線體 and thus
have a high capacity for oxidative phosphorylation  oxidative fiber
氧化性肌纖維

Most of the ATP such fibers produce is dependent upon blood flow to
deliver O2 and fuel 燃料(葡萄糖及脂肪酸)  these fibers are surrounded
by many small blood vessels 環繞許多小血管

Oxidative fibers also contain large amounts of an oxygen-binding
protein known as myoglobin 含有大量的氧氣結合蛋白肌紅素, which
increases the rate of O2 diffusion within the fiber and provides a small
store of O2  large amounts of myoglobin give the fibers a dark red
color  red muscle fiber 紅肌纖維
p301
Types of skeletal muscles fibers

In contrast, glycolytic fibers 醣解性肌纖維 have few mitochondria 較少
的粒線體 but possess a high concentration of glycolytic enzymes 較多
的醣解性酵素 and a large store of glycogen 較多的肝醣儲存

Corresponding to their limited use of O2 較少使用氧氣, glycolytic fibers
are surrounded by relatively few blood vessels 較少的血管 and contain
little myoglobin 較少的肌紅素  pale color 淡色  white muscle fibers
白肌纖維

Three types pf skeletal muscle fibers can be distinguished
Table 9-3
p301-302
Figure 9-24
p302
Additional clinical examples

Poliomyelitis 脊隨灰質炎 is a viral 病毒的 disease that destroys motor
neurons 運動神經被破壞, leading to the paralysis of skeletal muscle
骨骼肌麻痺, and may result in death due to respiratory failure 呼吸衰竭

Involuntary tetanic contraction 不隨意的強直收縮 of skeletal muscles
produces muscle cramps 肌肉痙攣  nerve action potentials fire at
abnormally high rates 不正常的高頻率

The specific cause of this high activity is uncertain 不確定, but it is
probably related to electrolyte imbalances 與電解質不平衡有關 in the
extracellular fluid surrounding both the muscle and nerve fibers  overexercise 過度運動 or persistent dehydration 持續性脫水

Similar in symptoms to muscular cramping is hypocalcemic tetany
低鈣強直  when extracellular Ca2+ concentration falls to about 40% of
its normal value 當細胞外液(血液)鈣離子濃度低於40%正常值會有低鈣強直

Low extracellular Ca2+ increases the opening of Na+ channels in
excitable membranes, leading membrane depolarization and the
spontaneous firing of action potentials 當細胞外液(血液)鈣離子濃度
太低時，會增加納離子通道的打開，導致去極化及自發性動作電位的
產生，因此造成骨骼肌過度收縮
p308
Additional clinical examples

Muscular dystrophy 脊隨性肌萎縮 is associated with the progressive
degeneration of skeletal and cardiac muscle fibers 骨骼肌及心肌漸漸
退化萎縮, weakening the muscles 肌肉虛弱 and leading ultimately to
death from respiratory or cardiac failure 因呼吸或心衰竭而死亡

The recessive gene 隱性基因 responsible for a major form of muscular
dystrophy (Duchenne muscular dystrophy) has been identified on the
X chromosome  is a sex-linked 性聯遺傳 recessive disease

This gene codes for a protein known as dystrophin, which is either
present in a nonfunctional form 沒有功能 or absent 缺乏 in patients with
this disease  fibers subjected to repeated structural deformation 變形
during contraction are susceptible to membrane rupture and cell death

Myasthenia gravis 重症肌無力 is a collection of neuromuscular disorders
characterized by muscle fatigue and weakness that progressively worsens
肌肉疲乏虛弱且逐漸惡化 as the muscle is used

The most common cause is the destruction of nicotinic Ach receptor
proteins of the motor end plate, mediated by antibodies of a person’s
own immune system 因自體免疫所產生的抗體會逐漸將尼古丁
接受器破壞所致
p308
Smooth muscle

Two characteristics are common to all smooth muscles: they lack the
cross-striated banding pattern 缺乏橫紋 found in skeletal and cardiac
fibers, and the nerves to them are derived from the autonomic nervous
system rather than the somatic motor neurons 受自律神經系統調控，
而不是體運動神經
Structures of smooth muscles

Each smooth muscle cell is spindleshaped 紡錘型  length ranging from
50~400 mm  they are much smaller
than skeletal muscle fibers

Many individual smooth muscles are
generally interconnected to form sheetlike layers of cells 每個平滑肌細胞通常
彼此連接形成一片
Figure 9-32
p312
Structures of smooth muscles

Smooth muscle cells have a single
nucleus 單核 and have the capacity to
divide throughout the life of an individual

Smooth muscle cells have thick
myosin-containing filaments and thin
actin-containing filaments  although
tropomyosin is present in the thin
filaments, the troponin is absent 沒有

The thin filaments are anchored either to
the plasma membrane or to cytoplasmic
structures known as dense bodies 緻密體,
which are functionally similar to the Z line
in the skeletal muscle
細肌絲固定在細胞膜或緻密體上
Figure 9-33

The filaments are oriented slightly
diagonally to the long axis 延著橫軸輕微
傾斜的方式排列 of the cell
p312-313
Smooth muscles contraction and its control
Cross-bridge activation

Because smooth muscle lacks the calcium-binding protein troponin,
tropomyosin is never held in a position that blocks cross-bridge access
to actin 因為平滑肌缺乏troponin，因此tropomyosin並沒有佔住actin上橫橋
的結合位

Instead, cross-bridge cycling in smooth muscle is controlled by a
calcium-regulated enzyme 受到鈣離子調節酵素的控制 that
phosphorylates myosin 磷酸化肌凝蛋白  only the phosphorylated
form of smooth muscle myosin can bind to actin and undergo crossbridge cycling 只有磷酸化的肌凝蛋白才能與肌動蛋白結合進行橫橋週期

Calmodulin 攜鈣素, a calcium-binding protein 一種鈣離子結合蛋白, is
present in the cytoplasm of most cells and whose structure is related to that
of troponin 存在大多數細胞的細胞質中，其結構類似troponin

After a rise in cytosolic Ca2+  Ca2+ binds to calmodulin  the
complex binds to another cytosolic protein, myosin light-chain kinase
(MLCK) 肌凝蛋白輕鏈激酶, thereby activating the enzyme 當鈣離子濃度
增加，鈣離子結合攜鈣素後，進而與MLCK結合，而活化了MLCK
p313
Cross-bridge activation
細胞質內鈣離子濃度增加
活化的鈣離子-攜鈣素複合物
去活化的攜鈣素
活化的鈣離子-攜鈣素-MLCK
去活化的MLCK
磷酸化的橫橋有
能量結合細肌絲
未磷酸化的橫橋靠近粗肌絲
Figure 9-34
p314
Cross-bridge activation

Active MLCK the uses ATP to phosphorylate myosin light chains (MLC)
in the globular head of myosin 活化的MLCK會將肌凝蛋白球狀頭上的
輕鏈(MLC)磷酸化

Phosphorylation of myosin drives the cross-bridge away from the thick
filament backbone, allowing it to bind to actin 磷酸化的肌凝蛋白可驅動
橫橋離開粗肌絲骨架，而結合到actin上

A key difference here is that calcium-mediated changes in the thick
filaments turn on cross-bridge activity in smooth muscle, whereas in
striated muscle, calcium mediates changes in the thin filaments
在平滑肌，鈣離子造成粗肌絲的改變，打開橫橋週期；而在橫紋肌，鈣離子
是造成細肌絲的改變

The two roles of ATP in smooth muscle: splitting one ATP to transfer a
phosphate onto MLC starts a cross-bridge cycling, after which one ATP
per cycle is split (hydrolysis) to provide the energy for force generation

To relax 鬆弛 a contracted 收縮的 smooth muscle, myosin must be
dephosphorylated 去磷酸化  this is mediated by the enzyme myosin
light-chain phosphatase 肌凝蛋白輕鏈磷酸酶, which is continuously
activate in smooth muscle during periods of rest and contraction
p313
Figure 9-35
p315
Sources of cytosolic calcium

Two sources of calcium (Ca2+) contribute to the rise in cytosolic Ca2+
that initiates smooth muscle concentration: (1) the sarcoplasmic
recticulum (SR) and (2) extracellular Ca2+ entering the cell through
plasma-membrane Ca2+ channels 有兩種鈣離子來源可啟動平滑肌收縮：
ㄧ為漿質網內，ㄧ為細胞外的鈣離子經由細胞膜上的鈣離子通道打開進入

The total quantity of SR in smooth muscle is smaller than in skeletal
muscle, and it is not arranged in any specific pattern in relation to the
thick and thin filaments 平滑肌內漿質網的量較骨骼肌少，也沒有像骨骼
肌在粗及細肌絲旁有特定的排列，因此細胞內鈣離子儲存量較少

There are no T-tubules connected to the plasma membrane in smooth
muscle 平滑肌的細胞膜上也沒有橫小管可以啟動漿質網釋放鈣離子
p314
Sources of cytosolic calcium

In addition, second messengers released from the plasma membrane
(IP3), or generated in the cytosol (cAMP) in response to the binding of
extracellular chemical messengers (Ach or catecholamines) to
plasma-membrane receptors (muscarinic or a1, b2), can trigger the
release of Ca2+ from the more centrally located SR
此外，化學訊息傳導物與細胞膜上的接受器結合，產生次級
訊息傳導物，也可促進鈣離子釋放

Removal of Ca2+ from the cytosol to bring about relaxation is achieved
by the active transport of Ca2+ back into the SR as well as out of the
cell across the plasma membrane 將鈣離子主動運送回漿質網及細胞外，
鈣離子濃度降低，即造成鬆弛

In some smooth muscles, the cytosolic Ca2+ concentration is sufficient
to maintain a low level of basal cross-bridge activity in the absence of
external stimuli  smooth muscle tone 有些平滑肌在缺乏外在的刺激
下，即可維持一個低程度的橫橋活性，產生收縮，此稱為平滑肌張力
p315
Membrane activation



Many inputs to a smooth muscle plasma membrane can alter the
contractile activity of the muscle  all of these inputs influence contractile
activity by altering cytosolic Ca2+ concentration 有許多傳入訊息可改變
細胞內鈣離子濃度，進而影響平滑肌的收縮活性
In smooth muscle, depolarization
of the membrane opens voltagegated Ca2+ channels, producing
Ca2+-mediated rather than Na+mediated action potentials
在平滑肌，去極化造成鈣離子通道
打開，引發動作電位，與神經細胞
經由鈉離子通道引發動作電位不同
Table 9-5
In smooth muscle cytosolic Ca2+ concentration can be increased (or
decreased) by graded depolarizations (or hyperpolarizations) in
membrane potential, which increase or decrease in the number of open
Ca2+ channels 在平滑肌，去極化造成鈣離子通道打開的數目增加，過極化
造成通道打開的數目減少，而影響細胞質內鈣離子濃度，進而影響收縮
p315-316
Spontaneous electrical activity

Some types of smooth muscles generate action potentials
spontaneously in the absence of any neural or hormone input
有些平滑肌，在缺乏任何神經或賀爾蒙的刺激下，會自發性產生動作電位

The plasma membranes of such cells do not maintain a constant resting
potential 這些細胞的細胞膜上，並不會有固定的靜止膜電位

Instead, they gradually 漸漸地
depolarize 去極化 until they reach
the threshold potential 閾值電位
and produce an action potential
這些細胞會逐漸去極化，當到達閾值時
即可產生動作電位

The membrane potential change
occurring during the spontaneous
depolarization to threshold is known Figure 9-36
as a pacemaker potential
此自發性去極化的電位稱為節拍器電位
p316
Spontaneous electrical activity

Other smooth muscle pacemaker cells have a slightly different pattern
of activity 有些平滑肌的節拍器細胞產生另外一種不同的自發性 the
membrane potential drifts up and down due to regular variation in ion
flux across the membrane 膜電位規則性的往上往下  slow waves 慢波

Pacemaker cells are found
thought the gastrointestinal
tract, and thus gut smooth
muscle tends to contract
rhythmically even in the
absence of neural input
在整個消化道都有節拍器細胞，
因此消化道的平滑肌綜然在沒有
神經的刺激下，也可進行規律性
的收縮
Figure 9-36
p316
Nerves and hormones

The contractile activity of smooth muscles is influenced by
neurotransmitters released by autonomic nerve endings 自律神經末端

As the axon of a postganglionic autonomic neuron enters the region of
smooth muscle cells, it divide into many branches 許多分枝, each
branch containing a series of swollen regions 膨大區 known as
varicosities 囊節
自律神經纖維

Each varicosity contains
many vesicles filled with
neurotransmitters
囊節

Varicosities from a
single axon may be
located along several
muscle cells
粒線體
囊節
Figure 9-37
突觸小泡
p316-317
Nerves and hormones

Smooth muscle tension 張力 can be either increased or decreased by
neural activity  例如副交感神經興奮讓胃腸道平滑肌收縮，而交感神經
則讓胃腸道平滑肌鬆弛

A given neurotransmitter may produce opposite effects in different
smooth muscle tissues  例如norepinephrine在大多數的血管平滑肌作用
在a1接受器會造成收縮，但作用在支氣管平滑肌的b2接受器則造成鬆弛

Second messengers (IP3) can cause release of Ca2+ from the SR,
producing a contraction without a change in membrane potential
雖然動作電位會啟動平滑肌收縮，但在沒有動作電位下，次級訊息傳導物
也會引起收縮
Local factors

Local factors 局部因子, including paracrine agents 旁泌素, acidity,
oxygen concentration, osmolarity 滲透性, and the ion composition
離子組成 of the extracellular fluid, can also alter smooth muscle tension

Nitric oxide (NO) 一氧化氮 is one the most commonly encountered
paracrine agents that produces smooth muscle relaxation 鬆弛
p317
Types of smooth muscle
Single-unit smooth muscle

Many smooth muscles can be placed into one of two groups, based on
the electrical characteristic of their plasma membrane: single-unit and
multiunit smooth muscles 依電性特性不同，平滑肌可分單一單位平滑肌
及多單位平滑肌
自律神經纖維

The muscle cells in a single-unit smooth muscle
undergo synchronous activity 協同性的活性  this
occurs because each muscle cell is linked to adjacent
fibers by gap junctions 間隙聯合, which allow action
potentials occurring in one cell to propagate to other
cells by local currents

Some of the cells in a single-unit muscle are
pacemaker cells that spontaneously generate action
potentials 有些單一單位平滑肌為節拍器細胞

One additional characteristic of single-unit muscles is
that a contractile response can often be induced by
stretching the muscle 有些單一單位平滑肌可因肌肉受
拉扯而引發收縮
囊節
間隙聯合
Figure 9-38 p318
Types of smooth muscle
Multi-unit smooth muscle

Multiunit smooth muscles have no or few gap junctions  each
cell responds independently, and the muscle behaves as multiple
units 多單位平滑肌沒有或很少的間隙聯合，因此每個細胞都是受到
獨立的調控

Multiunit smooth muscles are richly innervated by branches of
the autonomic nervous system 許多自律神經系統的纖維分岔調控
 stretching does not induce contraction in this type of muscle
拉扯反應不會引起這類的肌肉收縮
p318
Table 9-6
單一單位
多單位
p319
p319
 Binding of norepinephrine or epinephrine to an a1 adrenergic receptor
triggers activation of the phosphatidylinositol second messenger system
 Alpha 1 adrenergic receptors are most located in vascular smooth
muscle  a1 agonist can be used to treat congestion
 Binding of norepinephrine or epinephrine to an a2 adrenergic receptor
triggers inhibition of the cAMP second messenger system, whereas
binding to a b adrenergic receptor triggers excitation of the cAMP
second messenger system
Activation of multiple receptors
by a single transmitter effects on
signal transduction

Coactivation of more than one receptor
subtype for norepinephrine can result
in second-messenger responses,
which are opposing 相反, additive 加乘,
or independent 獨立.

G-proteins shown for stimulatory (Gs),
inhibitory (Gi), and phospholipase (Gq).

NE, Norepinephrine; AC, adenylate
cyclase; ATP, adenosine triphosphate;
cAMP, cyclic adenosine
monophosphate; PLC, phospholipase
C; PIP2, phosphatidylinositol 4,5bisphosphate; IP3, inositol 1,4,5trisphosphate; DAG, 1,2-diacylglycerol.