PSL300

PSL300 – Muscle 1 & 2

• Skeletal Muscle
• Smooth Muscle
• Cardiac Muscle
Classification of Muscle
• Skeletal muscle
• Smooth muscle
• Cardiac muscle
Skeletal Muscle
• Activated by the somatic nervous system
• Motor neurons (motor neuron + associated muscle fibers = motor unit)
• Chemical signaling between motor neuron and skeletal muscle = Neuro-Muscular
Junction (NMJ)
• NMJ= the synapse between a motor neuron and a muscle fiber (motor neuron’s
axon terminal, muscle fiber)
• Contractile filaments in sarcomeres; striated
• Well developed sarcoplasmic reticulum (SR)
Skeletal Muscle
• Activated by the somatic nervous system
• Motor neurons (motor neuron + associated muscle fibers = motor unit)
• Chemical signaling between motor neuron and skeletal muscle = Neuro-Muscular
Junction (NMJ)
• NMJ= the synapse between a motor neuron and a muscle fiber (motor neuron’s
axon terminal, muscle fiber)
• Contractile filaments in sarcomeres; striated
• Well developed sarcoplasmic reticulum (SR)
Skeletal Muscle
• Activated by the somatic nervous system
• Motor neurons (motor neuron + associated muscle fibers = motor unit)
• Chemical signaling between motor neuron and skeletal muscle = Neuro-Muscular
Junction (NMJ)
• NMJ= the synapse between a motor neuron and a muscle fiber (motor neuron’s
axon terminal, muscle fiber)
• Contractile filaments in sarcomeres; striated
• Well developed sarcoplasmic reticulum (SR)
Skeletal Muscle
• Activated by the somatic nervous system
• Motor neurons (motor neuron + associated muscle fibers = motor unit)
• Chemical signaling between motor neuron and skeletal muscle = Neuro-Muscular
Junction (NMJ)
• NMJ= the synapse between a motor neuron and a muscle fiber (motor neuron’s
axon terminal, muscle fiber)
• Contractile filaments in sarcomeres; striated
• Well developed sarcoplasmic reticulum (SR)
Skeletal Muscle
• Muscle = group of fascicles
• Muscle fibers extend length of muscle from tendon to tendon
Skeletal Muscle Fiber
• Muscle fiber made up of myofibril
• Sarcolemma = Plasma membrane
Skeletal Muscle Fiber
• T-tubule system = Invaginations of
sarcolemma into muscle fiber
Skeletal Muscle Fiber
• Sarcoplasmic reticulum =
Intracellular organelle, Ca++ storage
Motor Unit
• The muscle fibers of a motor unit all
contract together
• The smoothness and precision of
movement depends on the number
and timing of motor units that are
activated
• Muscle contraction begins with small
motor units being activated first
Motor Unit Types
• The muscle fibers of a motor unit are
all of the same type (e.g. motor unit
1 in red = slow oxidative)
• There are 3 broad categories of
muscle fibers, and hence of motor
units
• These categories are based upon
their histochemical characteristics
Muscle Fiber Types
• Slow-twitch oxidative fibers
– Slowly contracting
– Many mitochondria
– Oxidative metabolism
Muscle Fiber Types
• Fast-twitch glycolytic fibers
– Fast twitch time
– Produce large amounts of tension
– Rapid fatigue
Muscle Fiber Types
• Small diameter motor neurons innervate slow oxidative fibers
• Large diameter motor neurons innervate fast glycolytic fibers.
• Small diameter motor neurons are more easily excited than are large diameter
motor neurons
Properties of NMJ
• Anatomy of the neuromuscular junction
– Terminal bouton = axon terminal (motor neuron)
– Motor end plate = specialized muscle membrane at junction
• All motor neurons release acetylcholine
• All synapses are excitatory
Properties of NMJ
• Anatomy of the neuromuscular junction
– Terminal bouton = axon terminal (motor neuron)
– Motor end plate = specialized muscle membrane at junction
• All motor neurons release acetylcholine
• All synapses are excitatory
Activities of the NMJ
• Activation of motor neuron depends on summation of EPSPs/IPSPs
Communication at the NMJ
1. Action potential arrives at terminal
bouton
2. Voltage-gated calcium channels
open
3. Calcium enters cell triggering
release of ACh
4. ACh diffuses across cleft and binds
to nicotinic receptors on motor end
plate
Communication at the NMJ
5. ACh binding triggers opening of
channels for small cations (Na and
K)
6. Net movement of positive charge in
> depolarization
7. Causes action potential in muscle
cell
8. Action potential spreads through
muscle causing contraction
Poisoning the NMJ
• The brain is largely protected from toxins in the blood by the ‘blood-brain
barrier’.
• Peripheral tissues, including muscle, are exposed to circulating toxins.
• Toxins that block the NMJ fall into 3 types:
Poisoning the NMJ
• Nicotinic receptor blocker
• Poison dart (Curare)
• Curariform drugs
Poisoning the NMJ
• Exocytosis blocker
• Botox
Poisoning the NMJ
• Ach-esterase inhibition
• Nerve gases
• pesticides
The Mechanism of Force Generation
• The crossbridge cycle: how muscles
generate force
Skeletal Muscle Fiber
• Thin filament is made up of actin
• Thick filament is made up of myosin
Structure of a Sarcomere
• Actin and myosin are organized in overlapping arrangement with respect to one
another in units called sarcomeres
Structure of a Sarcomere
• Muscle contraction = Sarcomere shortening
• Actin and myosin do not change length, instead slide past one another
Thick Myofilament
• Thick filament is made up of myosin molecules
• Myosin head contains actin binding site and ATP binding site
Thin Myofilament
• Thin filament is made up of 2 strands of actin molecules
• Actin molecule has a binding site for myosin
Troponin & Tropomyosin Actions
• No Calcium: troponin holds
tropomyosin over myosin binding
sites on actin
– No crossbridges form between actin
and myosin
– Muscle relaxed
Troponin & Tropomyosin Actions
• Calcium Present: binds to troponin,
causing movement of troponin,
causing movement of tropomyosin,
exposing binding sites for myosin on
actin
– Crossbridges form between actin and
myosin
– Cycle occurs, muscle contracts
Crossbridge Cycle
• Myosin head undergoes
conformation changes swiveling
back-and-forth
– High-energy form
• High affinity for actin
– Low-energy form
• Low affinity for actin
• Relies on ATP hydrolysis
Crossbridge Cycle
• Power stroke: myosin head moves
propelling thin filament toward
center of muscle (movement of oar
propelling boat)
• Thick and thin filaments detach (oar
breaks contact with water)
• Myosin head returns to initial
position (oar moved to new position,
cycle starts again)
Crossbridge Cycle
• With increase in Ca++, myosin head
and actin filament bind strongly
• Power stroke occurs, myosin head
moves propelling the thin filament
toward center of muscle
Crossbridge Cycle
• Myosin releases ADP at the end of
power stroke
Crossbridge Cycle
• Tight binding in the rigor state

Rigor mortis
Crossbridge Cycle
• ATP binds to myosin
• Myosin releases actin
Crossbridge Cycle
• Myosin hydrolyzes ATP
• Myosin head rotated to cocked
position
• Myosin binds weakly to actin
Crossbridge Cycle
• Power stroke begins when
tropomyosin moves off the binding
site
Excitation-Contraction Coupling
• Sequence of events whereby an action potential in the sarcolemma causes
contraction
• Dependent on neural input from motor neuron
• Requires calcium release
Excitation-Contraction Coupling
• Ach released from motor neurons
• Binding of Ach = Na+ entry, leading
to muscle AP
Excitation-Contraction Coupling
• AP in t-tubule = alteration of DHP
• DHP receptor opens RyR Ca++
release channel in sarcoplasmic
reticulum
• Ca++ enters cytoplasm
Excitation-Contraction Coupling
• Ca++ binds to troponin allowing
actin-myosin binding, power stroke
occurs
Termination of Contraction
• Calcium must leave the binding sites
• To remove calcium from cytosol
– Ca2+ ATPase in sarcoplasmic reticulum
– Transports calcium from cytosol into sarcoplasmic reticulum
Twitch Contraction
• A muscle twitch is a single contraction-relaxation cycle
• Rise-time and duration of twitch force varies with muscle fiber type
• To generate force you need to have many twitches working together
Twitch Contraction
• 3 phases of muscle twitch
– Latent period
– Period of contraction
– Period of relaxation
• Latent period
– Excitation-contraction coupling
occurring
• Period of contraction
– Intracellular Ca++ levels are high,
crossbridge cycling is occurring
• Period of relaxation
– Intracellular Ca++ levels fall,
eventually tension gradually falls to
zero
Twitch Contraction
• 3 phases of muscle twitch
– Latent period
– Period of contraction
– Period of relaxation
• Latent period
– Excitation-contraction coupling
occurring
• Period of contraction
– Intracellular Ca++ levels are high,
crossbridge cycling is occurring
• Period of relaxation
– Intracellular Ca++ levels fall,
eventually tension gradually falls to
zero
Twitch Contraction
• 3 phases of muscle twitch
– Latent period
– Period of contraction
– Period of relaxation
• Latent period
– Excitation-contraction coupling
occurring
• Period of contraction
– Intracellular Ca++ levels are high,
crossbridge cycling is occurring
• Period of relaxation
– Intracellular Ca++ levels fall,
eventually tension gradually falls to
zero
Summation and Tetanus
• In skeletal muscle, with increased AP
frequency, successive twitches fuse
with each other
• Contractile force rises
Summation and Tetanus
• Repeated stimulation = fuse into one continuous contraction called tetanus
Summation and Tetanus
• Muscle fatigue results in rapid decrease in tension
Smooth Muscle
• Found in internal organs, blood vessels
• Examples of smooth muscles: vasculature, GI tracts, urinary, reproductive, and
respiratory tracts, pupil, etc…
• Not arranged in sarcomeres
• Under involuntary control by ANS
Smooth Muscle
• Must operate over a range of lengths
• Layers may run in several directions
• Contracts and relaxes much more
slowly
• Uses less energy
• Sustains contractions for extended
periods
Classification of Smooth Muscle
• By location
– Vascular, gastrointestinal, urinary, respiratory, reproductive, ocular
• By communication with neighboring cells
– Single-unit smooth muscle, or visceral smooth muscle
– Multi-unit smooth muscle
Single-Unit Smooth Muscle
• Single-unit smooth muscles
– Found in the Intestinal tract and
Blood vessels etc…
– Exhibits spontaneous activity (but
also activated by the ANS)
– Able to actively exert tension in
absence of external stimulation
Multi-Unit Smooth Muscle
• Multi-unit smooth muscles
– Found in large airways and arteries
etc…
– Each fiber acts individually
– Heavily innervated
– Generally, contracts only when
nervous supply is stimulated
Excitation-Contraction Coupling
• Lacks specialized receptor regions
• Ca2+ is from the extracellular fluid and sarcoplasmic reticulum
• Ca2+ initiates a cascade ending with phophorylation of myosin light chain and
activation of myosin ATPase
Excitation-Contraction Coupling
• Opening of calcium channels in
plasma membrane
• Calcium triggers release of calcium
from sarcoplasmic reticulum
• Calcium binds to calmodulin
• Ca-Calmodulin activates MLCK
• MLCK phosphorylates myosin
• Crossbridge cycling
Excitation-Contraction Coupling
• Opening of calcium channels in
plasma membrane
• Calcium triggers release of calcium
from sarcoplasmic reticulum
• Calcium binds to calmodulin
• Ca-Calmodulin activates MLCK
• MLCK phosphorylates myosin
• Crossbridge cycling
Relaxation of Smooth Muscle
• Phosphatase removes phosphate from myosin
• Calcium removed from cytoplasm
– Ca-ATPase
– Ca-Na counter transport
Cardiac Muscle
• Contractile cells and conductile cells
• Contractile filaments in sarcomeres; striated
• Intermediate development of SR
• Gap-junctions for synchronous beat
• Activity modulated by ANS (unlike skeletal muscle = somatic nervous system)
Cardiac Muscle - AP
• AP duration 300ms in ventricles
• AP plateau due to slow Ca2+ channels allows time for forceful contraction from
single AP
• Plateau allows muscle contraction to last 300ms (20-50x longer than in skeletal
muscle)
• AP shape and duration reflects changing permeability to Na+, Ca2+
Cardiac Muscle - AP
• Cardiac contractile cell AP last for
almost as long as the contraction and
relaxation
Cardiac Muscle Contraction
• One way to increase force of
contraction:
• Unable to increase force of
contraction by motor unit
recruitment or by enhanced
excitation/contraction coupling
• Unable to increase force of
contraction by increasing stimulation
frequency to tetanus
• Increase force of contraction by
increasing muscle length (Starling
law)
Excitation-Contraction Coupling
• Significant Ca2+ source from ECF, rest
from SR
• Contractile proteins in presence of
increased cytosolic [Ca2+] power
contraction (systole)
• Ca2+ pump in the SR removes Ca2+
from cytosol allowing for relaxation
(diastole)
• Na+/Ca2+ membrane exchange
removes Ca2+ from cytosol allowing
for diastole
Thank You!