Physiology of Muscle
Humaryanto
TIPE OTOT
Otot Skeletal
(lurik/striata)
Otot Jantung
(lurik/striata)
Otot Polos (polos)
(GI, VU, Vascular)
Extrafusal Muscle Fibers
Striate muscle
Force for limb movements
– flexion - closes joint
– extension - opens joint
Contract or relax ~
OTOT SKELETAL
40% BB tubuh
Fungsi : mengatur posisi
dan gerak rangka
Melekat ke tulang melalui
tendo
Origo : perlekatan pada
bag. proksimal, bersifat
stasioner
Insersio : perlekatan pada
bag. distal, bersifat mobil
TIPE OTOT SKELETAL
Berdasarkan kecepatan kontraksi dan daya
tahan terhadap fatigue.
Fast-twitch glycolitic fibers (putih)
Fast-twitch oxidative fibers (merah)
Slow twitch oxidative fibers (merah)
Setiap orang punya 3 tipe otot, tapi berbeda
pada komposisi dominan
(Jauhari Johan vs John Murray/ Ben Johnson)
Type 1 Fibers
Slow fibers
dark red
– slow, sustained contraction
– slow to fatigue
Aerobic metabolism
– many capillaries & mitochondria
– oxygen required for ATP synthesis
– myoglobin
gives dark red appearance ~
Type 2b Fibers
Fast fatigable fibers
white fibers
– rapid, brief contraction
– fast to fatigue
– produce about 10x force of Type 1
Anaerobic metabolism
– fewer capillaries & mitochondria
– ATP generated by glycolysis
– lactic acid buildup ~
Type 2a Fibers
Fast fatigue-resistant fibers
pale red
–
–
–
–
properties intermediate to types 1 & 2b
rapid, brief contraction
slow to fatigue
produce least force
Aerobic & Anaerobic metabolism
– many capillaries & mitochondria ~
Neuromuscular Junction
Synapse between neuron & effector
Cholinergic (ACh)
– nicotinic receptors
Motor end-plate
– postsynaptic membrane
– folds packed with receptors
increased surface area ~
Global view of a
neuromuscular
junction:
1. Axon
2. Motor end-plate
3. Muscle fiber
4. Myofibril
Detailed view of a
neuromuscular junction:
1. Presynaptic terminal
2. Sarcolemma
3. Synaptic vesicle
4. Nicotinic acetylcholine
receptor
5. Mitochondrion
Mechanism of action
Upon the arrival of an action potential at the axon
terminal, voltage-dependent calcium channels open and
Ca2+ ions flow from the extracellular fluid into the motor
neuron's cytosol. This influx of Ca2+ triggers excitationcontraction coupling, a biochemical cascade that
causes neurotransmitter-containing vesicles to fuse to
the motor neuron's cell membrane and release
acetylcholine into the synaptic cleft.
Acetylcholine diffuses across the synaptic cleft and binds
to the nicotinic acetylcholine receptors that dot the motor
end plate.
The receptors are ligand-gated ion channels, and when
bound by acetylcholine, they open, allowing sodium and
potassium ions to flow in and out of the muscle's cytosol,
respectively.
Mechanism of action
Because of the differences in electrochemical gradients
across the plasma membrane, more sodium moves in
than potassium out, producing a local depolarization of
the motor end plate known as an end-plate potential
(EPP).
This depolarization spreads across the surface of the
muscle fiber into transverse tubules, eliciting the release
of calcium from the sarcoplasmic reticulum, thus
initiating muscle contraction.
The action of acetylcholine is terminated when the
enzyme acetylcholinesterase degrades the
neurotransmitter and the unhydrolysed neurotransmitter
diffuses away
Neurotransmitters and
Neuromodulators
Neuromodulators modify the postsynaptic cell's response to
neurotransmitters or change the presynaptic cell's synthesis, release or
metabolism of the neurotransmitter.
Acetylcholine (Ach)
Major neurotransmitter. Fibers that release ACh are called cholinergic
fibers. Acetylcholine is degraded by the enzyme, acetylcholinesterase.
Biogenic Amines
Biogenic amines are neurotransmitters containing an amino group.
Catecholamines such as dopamine, norepinephrine and epinephrine,
serotonin. Nerve fibers that release epinephrine and norepinephrine are
called adrenergic and noradrenergic fibers respectively.
Neurotransmitters and
Neuromodulators
Amino Acid Neurotransmitters
Amino acid neurotransmitters are the most prevalent
neurotransmitters in CNS. Glutamate, aspartate GABA (gamma
aminobutyric acid), glycine,
Neuropeptides
Neuropeptides are composed of two or more amino acids. Neurons
releasing neuropeptides are called peptidergic. Beta-endorphin,
dynorphin, enkephalins.
Nitric oxide, ATP, adenine also act as neurotransmitters.
Neuroeffector Communication
Many neurons of peripheral nervous system end at neuroeffector
junctions on muscle and gland cells. Neurotransmitters released by
these efferent neurons then activate the target cell.
Muscle Contraction
AP generated in muscle fiber (cell)
Ca++ released from internal stores
Muscle fiber contracts
– continues while Ca++ & ATP available
Relaxation
– Ca++ sequestered by active transport ~
Muscle Fiber Structure
Multinucleated
– fusion of multiple precursor cells
Sarcolemma Excitable membrane
Myofibrils: contractile units
Sarcopasmic reticulum (SR)
– sequesters Ca++
T tubules
– AP from sarcolemma to SR
– like inside-out axons ~
Miofibril  struktur kontraksi otot
1 Serat otot, tdd: ribuan miofibril
1 miofibril tdd:
Aktin & miosin (protein kontraksi)
Troponin & tropomiosin (protein pengatur)
Titin & nebulin (protein asessoris besar)
Miosin  thick filament, punya kepala
Motor protein, E kimia  E mekanik, mgd ATP-ase (hidrolisis)
Aktin  thin filament, melekat troponin & tropomiosin
Titin  molekul elastis (protein terbesar)
 stabilitas & elastisistas otot
Nebulin  penyanggah aktin
Sarcoplasmic
Reticulum
Myofibrils
T tubules
Sarcolemma
Myofibril: structure &
function
Sarcomeres
– repeating sections
Z lines
dividers between sarcomeres
thin filaments anchored to Z lines
– actin & troponin
Thick filaments between thin filaments
– myosin
Contraction:filaments slide by each other
~
Z line
Thin filaments
Sarcomere
Z line
Thick
Filaments
KONTRAKSI OTOT
Menghasilkan force / gaya  muscle tension
Melawan beban/ load
Memerlukan energi (dari ATP)
Pencetus kontraksi otot
1. Neuromuscular junction :
Rangsang somatik  rangsang listrik
2. Excitation-contraction coupling
Potensial aksi  signal Ca++  siklus kontr-relaks
SIKLUS KONTRAKSI DAN RELAKSASI
 Sliding filaments theory
Contraction
Excitation-contraction coupling
Myosin “heads” crossbridges w/ actin
– Ca++ dependent
– binds to troponin, reveals binding site
Myosin head rotates
– “ratchets” actin inward ~
Contraction
ATP binds to myosin ---> detachment
– cocks myosin ---> binds again
– rigor mortis: no ATP
fibers remain crosslinked
Repeats as long as Ca++ present
– sequestered via active transport ~
SLIDING FILAMENT THEORY
Serat otot memendek (overlapping thick & thin filament)
Sliding aktin terhadap miosin
Gaya dari crossbridge miosin mendorong aktin
(power stroke)
Crossbridge miosin mendorong aktin menuju pusat
sarkomer
Setelah power stroke kepala miosin melepas aktin untuk
mengikat bagian aktin yang lain, demikian seterusnya
jadi siklus.
Analogi : menarik tambang.
In the absence of calcium ions, tropomyosin
blocks access to the mysosin binding site of
actin.
When calcium binds to troponin, the positions of
troponin and tropomyosin are altered on the the
thin flament and myosin then has access to its
binding site on actin.
Myosin hydolyzes ATP and undergoes a
conformational change into a high-energy state.
The head group of myosin binds to actin forming
a cross-bridge between the thick and thin
filaments.
Role of Ca+2 in Muscle Contraction
Ca+2
Ca++
Ca++
* Actin-binding sites are
exposed as a result of
Ca+2 binding to troponin
complex that causes a
conformational shift of
tropomyosin
The energy stored by myosin is released, and
ADP and inorganic phosphate dissociate from
myosin.
The resulting relaxation of the myosin molecule
entails rotation of the globular head, which
induces longitudinal sliding of the filaments.
When the calcium level decreases, troponin
locks tropomyosin in the blocking position and
the thin filament slides back to the resting state.
Sliding-Filament Mechanism
Muscle contraction is produced by cross bridge cycles.
A cycle has 4 steps:
(1) Energizing of myosin cross bridge
A + M•ATP —> A + M*•ADP•Pi (ATP is energizer here)
(2) Attachment of cross bridge to a thin filament
A + M*•ADP•Pi —> A•M*•ADP•Pi
(3) Movement of cross bridge, producing tension
A•M*•ADP•Pi —> A•M + ADP + Pi
(4) Detachment of cross bridge from thin filament
A•M + ATP —> A + M•ATP (ATP is modulator here)
Movement of the cross bridges make the overlapping
thick and thin filaments slide past each other (they do not
change in length) to produce a contraction.
Actin Myofilament
During contraction,
calcium binds to
troponin
Covers actin-binding
sites at rest
Cross-Bridge Formation
Cross-Bridge Cycle
Cross-bridge Cycle
This animation by Mike Geeves,
Laboratory of Molecular Biology in the UK
and the Cambridge Institute for Medical
Research
SIKLUS KONTRAKSI
1.
2.
3.
4.
5.
6.
Rigor state: Kepala miosin terikat dg molekul G-aktin.
ATP menempel ke miosin, kepala miosin lepas dari
aktin.
Hidrolisis ATP: jadi ADP + Pi (masih menempel)
Miosin melekat ke G-aktin yang baru, energi dari
pecahnya ATP, saat ada potensial energi di kepala
miosin untuk power stroke.
Pi lepas & power stroke: Kepala miosin berotasi
mendorong aktin mendekati pusat sarkomer
(crossbridge tilting)
ADP lepas: kepala miosin tetap melekat ke aktin, siap
untuk siklus berikut bila ada ATP yang baru
Excitation-Contraction Coupling
Excitation-Contraction Coupling
Excitation-Contraction (EC) Coupling:
1. An AP travels down a motor (somatic neuron).
2. The AP causes the release of the neurotransmitter
acetylcholine into the synapse at the neuromuscular
junction.
3. The acetylcholine binds to the acetylcholine receptors
on the muscle fiber and cause an EPSP.
4. If the EPSP reaches threshold, an AP is produced on
the sarcolemma of the muscle fiber. Meanwhile, the
acetylcholine attached to the receptor is destroyed.
5. The AP travels rapidly along the sarcolemma and
enters the fiber at every t-tubule.
Excitation-Contraction Coupling
6. As the AP travels through the t-tubule, it causes the Ca++ gates
to open and Ca++ flows from the SR into the sarcoplasm. The
Ca++ gates close when the AP ends.
7. The increased [Ca++] in the sarcoplasm results in Ca++ binding
to troponin. This induces an allosteric change, the tropomyosin is
pulled out of the way and steric inhibition is removed. The result
is crossbridges begin to form, rotate and break (provided there is
plenty of ATP).
8. Cross-bridge cycling continues as long as sarcoplasmic [Ca++]
remains high.
9. However, if the Ca++ gates close, the action of the Ca++
ATPase (pump) begins to predominate and sarcoplasmic
[Ca++]] drops. When it drops low enough, the troponin loses its
Ca++ and changes shape the next time a crossbridge is not in
the way. Steric inhibition is quickly re-established and the muscle
contraction is over.
Exitation-Contraction Coupling
Dirangsang oleh asetilkolin/achetylcholine
Tahap:
Asetilkolin (Ach) lepas dari motor neuron
somatik
Ach merangsang potensial aksi serat otot
PA, m’rsg Ca++ lepas dr Ret.Sarkoplasma
Ca++ me’ikat troponin dan m’rsg kontraksi
DHP:
Dihydropiridine
Saat PA:
Ca  100x
Relaksasi:
Ca masuk RS
krn enzim
Ca-ATP-ase
PERIODE KONTRAKSI/ TWITCH
1. Periode Laten
(Antara potensial aksi-kontraksi)
2. Periode kontraksi
3. Periode relaksasi
Lama periode kontraksi tergantung tipe otot
SUMBER ENERGI KONTRAKSI
ATP (Adenosine Tri Phosphate)
1. Kontraksi: gerakan crossbridge
2. Relaksasi: Ca++ masuk lagi ke RS
3. Relaksasi: melepas ikatan aktin dan miosin
4. Diluar periode kontraksi : restore Na-K
SUMBER ATP
1. Konversi posfo-kreatin (8 twitch)
2. An-aerobik glikolisis
3. Posforilasi-oksidatif
KELELAHAN OTOT
Fatigue:
Kondisi dimana otot tidak mampu lagi
melakukan / mempertahankan kontraksi
Jenis Fatigue:
Sentral: SSP
Perifer: NM-Junction – elemen kontraksi
E/ >>  elemen kontraksi
Lelah Sentral
Kelelahan
Perifer
SSP
Psikologis
Refleks Proteksi
Asidosis
(as. Laktat)
NM-Junction
 Pelepasan
Ggn.
Neurotransmitter Neuromuskuler
dan sensitivitas
(Ach )
reseptor
Excitationcontraction
coupling
Perubahan
membran
potensial
Gangguan
elektrolit
(Hipokalemia)
Ca++ signal
 Pelepasan Ca
& interaksi dg
troponin
Pi
Kontraksirelaksasi
 PCr, ATP,
glikogen
 H+, Pi, laktat
Pi
Daya kontraksi (tension) maksimal tjd pada
panjang sarokomere yang optimal
Tension juga meningkat bila stimulus dilakukan
berulang kali sebelum mencapai relaksasi
maksimum (Stimulus Summation)
Akan tetapi, bila stimulus
(potensial aksi) berlangsung
terus menerus dg cepat
(frekuensi tinggi), tanpa fase
relaksasi  terjadi Tetanus
Tetanus
-Komplet/ fused
-Inkomplet / unfused
Muscle Adaptation to Exercise
Increased amount of contractile activity
(exercise) increases size (hypertrophy) of
muscle fibers and capacity for ATP production.
Low intensity exercise affects oxidative fibers,
increasing the number of mitochondria and
capillaries.
High intensity exercise affects glycolytic fibers,
increasing their diameter by an increased
synthesis of actin and myosin filaments, and an
increased synthesis of glycolytic enzymes.
Speed of Muscle Contraction
Varies by Fiber Type
MOTOR UNIT
Unit dasar kontraksi, tdd: bbrp serat otot + motor
neuron somatik
Motor neuron mencetuskan potensial aksi 
kontraksi 1 motor unit.
1 motor neuron  bbrp otot; 1 serat otot
dipersyarafi 1 neuron
Otot kecil (gerak halus; tangan, wajah) 
1 motor unit = 3-5 serat otot
Otot besar (gerak kasar; tungkai, trunkus) 
1 motor unit = 100an- 1000an serat otot
Motor Pools & Motor Units
Motor Pool
all a motor neurons that innervate a single
muscle
An a motor neuron and
all the muscle fibers that it innervates
1:3 to 1:100
fewer muscle fibers ---> finer control
– 3 types based on speed of contraction &
fatigue ~
Types of Motor Units
Most muscle contain both slow- & fasttwitch fibers
– ratio depends on function
e.g. ankle extensors
– Soleus active during standing
hi ratio of slow fibers
– Medial Gastrocnemius: active during running
& jumping
hi ratio of fast fibers ~
Variasi gradasi, gaya & durasi kontrksi
 ditentukan oleh :
Jumlah & jenis motor unit yang aktif
(‘Recruitment’ dikontrol oleh SSP)
Kontraksi lemah  SSP m’rsg sedikit motor unit
Motor unit yang t’rsg Ix nilai ambang rendah  slowtwitch
Stimulus   m’rsg motor neuron dg nilai ambang tinggi
 fast-twitch
 Jumlah motor unit  daya kontraksi 
Asynchronous Recruitment
Pada kontraksi lama, SSP m’rsg bbrp motor unit scr
bergantian  1 serat kontraksi, serat lain istirahat
Hanya terjadi pada kontraksi sub-maksimal, why ?
BIOMEKANIKA GERAK TUBUH
Fs otot: menggerakkan rangka
KONTRAKSI ISOTONIK (Iso;=, teinein; stretch)
Kontraksi  gaya + menggerakkan beban
 Sarkomer menarik beban dan serat elastis
Konsentrik arah gerak = pemendekan otot
Eksentrik arah gerak = pemanjangan otot
 >> m’rusak otot (DOMS)
KONTRAKSI ISOMETRIK (Iso;=, metric;ukuran)
Kontraksi  gaya + tanpa menggerakkan beban
 Sarkomer otot hanya menarik serat elastis
USAHA OTOT
Lever/ lengan  dibentuk oleh rangka
Fulcrum/ sumbu  dibentuk sendi
W=Fxd
W (otot) = W (beban)
Insersi bisep 5 cm dari siku
Panjang lengan 20 cm
Berat beban 5 kg
Berapa usaha otot bisep
mengangkat beban ?
Semakin dekat insersi ke fulcrum
 Gerak semakin luas
Refleks Otot Skeletal
Berfungsi utk:
1. Mengatur keseimbangan
2. Gerak spesifik (keselamatan)
3. Optimalisasi gerak
Komponen Refleks
1.Reseptor sensoris (proprioceptors)
Spindle otot, organ tendo Golgi & reseptor sendi
2. Neuron sensoris (transfer input)
3. SSP
4. Motor neuron somatik (alfa motor neuron)
5. Serat otot (serat ekstrafusal)
Reseptor Sendi
Terdapat di kapsul sendi dan ligamen
Distimulasi oleh distorsi mekanik krn
perubahan sudut, beban dan posisi sendi
& tulang
Pusat pengaturan di cerebellum
Spindle Otot
Reseptor regangan otot
Mengirim impuls ke Med. Spinalis & otak
Responsif thd perubahan panjang otot
1 otot memiliki bbrp spindle otot, kec,
rahang
Terletak di sisi dalam otot ekstrafusal,
mengelilingi otot intrafusal
Akibat dari rangsangan menghasilkan
refleks kontraksi
Organ Tendo Golgi
Terletak di sambungan tendo dan otot
Responsif terhadap tegangan otot
Menghasilkan refleks relaksasi
Terdiri dari ujung syaraf bebas
Refleks menghambat interneuron di MS,
interneuron menghambat alfa motor
neuron sehingga kontraksi berkurang.
Knee Jerk reflexes;
merangsang spindle otot
Flexion reflexes;
menghindari bahaya
Movement Disorders of
Muscle
Duchenne’s Muscular Dystrophy
Muscular Dystrophies
– wasting away of muscles
– metabolic / structural abnormalities
Duchenne’s
– best understood
– young boys ~
Duchenne’s Muscular Dystrophy
Cause
– hereditary - maternal X chromosome
– single gene ---> protein
dystrophin
– maybe involved in Ca++ regulation
Treatment
– Inject dystrophin or mRNA
– Gene therapy promising for muscles ~
Myasthenia Gravis
Severe muscle weakness
– rapid fatigue following exercise
Develops in people of all ages
– Most common: women in 30s
– Risk of respiratory paralysis
Autoimmune disorder
– body develops antibodies for ACh-R
– reduces synaptic transmission ~
Myasthenia Gravis: Treatment
AChE inhibitors
– ¯ degradation of ACh
– narrow therapeutic window
– too much ACh ---> paralysis
Reduce immune response
– remove thymus
– filtering antibodies from blood
temporary ~