Download Muscles

Muscles
Magdalena Gibas-Dorna MD, PhD
Dept. of Physiology
University of Medical Sciences
Poznań, Poland
Please read about muscle
physiology from:



Pocket Companion to Guyton and Hall
Textbook of Medical Physiology (Guyton
Physiology)
Handouts
Ppt provided
Usually: skeletal = attached to bones
visceral = line internal organs
cardiac = in heart
Voluntary
control
Skeletal
muscle
Striated
structure
Smooth
structure
Cardiac
muscle
Visceral
muscle
Involuntary
control
Striated (microscopically striped) = skeletal
+ cardiac
Smooth (unstriped) = visceral
Voluntary
control
Skeletal
muscle
Striated
structure
Smooth
structure
Cardiac
muscle
Visceral
muscle
Involuntary
control
Voluntary = must receive CNS stimulation
Involuntary = can contract on its own
Voluntary
control
Skeletal
muscle
Striated
structure
Smooth
structure
Cardiac
muscle
Visceral
muscle
Involuntary
control
SKELETAL MUSCLE
Skeletal Muscle
Skeletal muscle cells generate much
force and must generate much energy
to move bone.
Resting potential: -80 to –90mV
Tendon
Velocity
7 x 5/35
=1 cm/s
Muscle
Force
10 x 35/5
=70 kg-wt
Tendons
Bicepts
(agonist
muscle)
Origin
Tricepts
(antagonist
muscle)
Flexion
Fulcrum
for
lever
10 kg
Hand
force
10 kg-wt
Insertion
Extension
5 cm
35 cm
Lever ratio
5:35 or 1:7
Antagonistic pair
of muscles at a
joint:
flexion (close
joint), extension
(open joint)
Muscles can only contract
(pull), they cannot push
Myosin heads are the crossbridges; tails
align and point to thick filament center.
(C) Functional assembly of myofilaments
Thick filaments (myosin)
Thin filament
(actin, troponin
And tropomyosin)
Crossbridgefree region
Functional overlap
region
Functional overlap
region
Thin and thick filaments
A-band = myosin thick filaments (+ thin
overlap); I-band = only actin thin filaments.
Z line
Longitudinal
Thick
filaments
Cross sectional
Z line
Thin
filaments
Thick
Filaments
at M line
Thick and thin
filaments
Relaxed sarcomere
M
Z line
Z line
line
I band
I band
H
zone
A band
I band
I band
Contracted sarcomere
Z line holds thin filaments; M line holds
thick; H zone = thick filaments, no overlap
.
Z line
Longitudinal
Thick
filaments
Cross sectional
Z line
Thin
filaments
Thick
Filaments
at M line
Thick and thin
filaments
Relaxed sarcomere
M line
Z line
Z line
I band
I band
H zone
A band
I band
I band
Contracted sarcomere
Z line
Longitudinal
Thick
filaments
Cross sectional
Cyclic “rowing” of thick
filaments over thin
shortens I-band, H
zone, but A band is
constant.
During muscle
contraction the amount
of overlap between
thick and thin filaments
changes.
Z line
Thin
filaments
Thick
Filaments
at M line
Thick and thin
filaments
Relaxed sarcomere
M
Z line
Z line
line
I band
I band
H
zone
A band
I band
I band
Contracted sarcomere
Skeletal muscle
TYPES OF CONTRACTION
Types of contraction
Frequency of stimulation
 Single muscle twitch (in
vitro)
 Tetanic
incomplete
complete
Type of work
 Isotonic
 Isometric
 Auxotonic
Daily activity of skeletal muscles is based on auxotonic
tetanic contractions
Isometric and isotonic
contractions
Agonist tenses but
does not shorten
Force of muscle contraction
equals counterforce of weight
ISOMETRIC CONTRACTION
Force of muscle contraction
equals counterbalance of
opposing muscle contraction
Opposing muscles
contract simultaneously
No movement
States of contraction
States of relaxation
Greater force of
muscle contraction
No movement
Agonist shortens
Lesser counterforce of weight
Antagonist relaxes
by reflex action
ISOTONIC CONTRACTION
Movement takes
place
Isometric contractrion – the muscle length remains constant while the muscle develops tension
Isotonic contraction – the muscle force remaines constant while the muscle shortens
Measuring the force of isometric contaction.
The muscle does not do any external
contraction.
Oscilloscope
Length scale
Rigid support
Length adjustment
Length
Muscle
(isometric
contraction)
Force
Time
Force transducer
Stimulator
In a mixed contraction, the contraction is
isometric until the load is lifted, and then it is
isotonic.
Oscilloscope
Length
Length transducer
Rigid support
Lever
Length
Pivot
Force
Length adjustment
Afterload
support
Muscle
(isotonic
contraction)
Time
Stimulator
Force transducer
Auxotonic contractions


Skeletal muscles usualy develop auxotonic contractions
Isometric contraction (stretch of elastic elements and
development of tension)
tension (force) of muscle
equals counterforce of weight (load) contraction with
constant tension of a muscle (isotonic contaction)
The weight that muscle
lifts during an isotonic
contraction is called
the afterload
Isometric and isotonic contractions
The isometric length-tension curve has a peak
force (tension) at the muscle’s optimal resting
length.
F
O
R
C
E
Total
Active
Passive
Length (cm)
WHOLE MUSCLE
F
O
R
C
E
Length (microns)
SINGLE SARCOMERE
At short muscle lengths, filaments
interfere with one another, and
activation is poor.
F
O
R
C
E
Total
Active
Passive
Length (cm)
WHOLE MUSCLE
F
O
R
C
E
Length (microns)
SINGLE SARCOMERE
At long
muscle
lengths,
fewer myosin
crossbridges
can interact
with thin
filaments.
Skeletal muscle action potentials (Na+/K+based) propagate as in an unmyelinated axon.
T tubules propagate the action potentials to
the interior of the cell for rapid activation.
Sarcolemma
Longitudinal sarcoplasmic reticulum
T-tubules
Terminal
cisternae
Myofilaments
T-tubule AP  open DHP receptor  open
SR Ry recept.  Ca++ release  contraction
Sarcolemma
Longitudinal sarcoplasmic reticulum
T-tubules
Terminal
cisternae
Myofilaments
Relaxation occurs when Ca++ is pumped
back into SR (ATP-dependent Ca++ pump).
Sarcolemma
Longitudinal sarcoplasmic reticulum
Myofilaments
T-tubules
Ca++ binds to troponin-C; tropomyosin
shifts; myosin interacts with actin.
Actin
Tropomyosin
Binding sites
exposed
Covered
Ca2+
Ca2+
Troponin
complex
Tropomyosin
Glycolysis (the anaerobic pathway) is
cytoplasmic, and yields relatively little ATP.
Consumption
of ATP
Replenishment
of ATP
ATP
supply
ATP
Glycolysis
Lactic
Glycogen
acid
Glucose
With oxygen, mitochondria breakdown
glycolysis products for much more ATP.
Consumption
of ATP
Replenishment
of ATP
O2
Fatty
acids
Amino
ATP
acids
Citric
acid cycle
ATP
supply
80% of energy produced during
contraction is heat, which must be
eliminated, or used.
Factors that affect myoneural
transmission
Factors that block myoneural
transmission
Presynaptic:



Infantile Botulism
Weakness, hypotonia, enlarged
pupils
Too many Mg2+ or too
few Ca2+ near the axon
terminal ( Ach release)
Hemicholiniums - block
the uptake of choline
into cholinergic nerve
terminals ( synthesis of
Ach)
Botulinum toxin blocks
the release of ACh from
the presynaptic
membrane
Botox – initially used for Sclerosis multiplex
treatment
The effect lasts 6 months. Side effects include: bruises,
rush, headakes, ptosis, vomiting
Factors that block myoneural
transmission
Postsynaptic:
Curare grows as a large
liana, or vine, found in
the canopy of the South

American rainforest

Curare – competition with
ACh; resistant to AChesterase (no depol.)
Succinylcholine –
depolarizing muscle relaxant;
The prolonged stimulation of
the ACh receptor results first
in disorganized muscle
contractions, then in
profound relaxation (the end
plate membranes remain
depolarized)
Stimulators of neuromuscular
junction


Physostigmine –
reversible
cholinesterase
inhibitor; causes
muscle spasm
Diisopropyl
fluorophosphate
(DFP) „nerve” gas
poison
Myasthenia gravis


Treatment:

-drugs inhibiting acetylcholinesterase
(eg. Physostigmine)
-drugs suppressing the production of
abnormal antibodies
-plasma exchange or gamma globulins
decrease of acetylcholine
receptors at the level of
neuromuscular junction
anti-AChR antibodies are
involved
Symptoms iclude: Increased
fatigue and weakness of
voluntary muscles particularly:
chewing, swallowing, talking, eyelids,
eye movements, facial expressions,
arms, hands, fingers, legs, neck,
breathing
Cardiac muscle
Cardiac Muscle
Cardiac muscle cells are small, branched,
and connected by intercalated discs.
Intercalated
disc
Cardiac muscle

Bundles of
myofibrils run the
length of the cells,
and SR and Ttubule system are
present
Cardiac muscle

The sarcomeres are organized in the same
way as they are in skeletal muscle
Muscle length also influences contraction
force, as it does in skeletal muscle.
Heart does not require innervation; initiates
own contraction, cell-cell communication.
Inotropic agents – increase internal supply
of calcium (digitalis, epinephrine)
Heart muscle contractions depend on Ca
ions influx both from extra- and
intracellular sources
Calcium channel blockers – reduce
strength of contractions
Shortening and force
development

Summation and tetanus are not possible (Cardiac
cells have long AP and long twitches and do not show temporal
summation)


The sarcomere length before contraction depends
on how much blood has entered the heart
The force of contraction can vary at a given
sarcomere length if the amount of Ca2+ entering
the cell is changed. This also is under physiologic
control
Smooth muscle
Smooth Muscle
Nucleus
Cells are small,
Rough
spindle-shaped,
Endoplasmic
reticulum
connected by gap
Glycogen
granules
junctions, and
Mitochondria have connective
tissue.
Thin filament
Thick filament
Dense
bodies
Plasma
membrane
Smooth muscle
layers are arranged
to squeeze and
shorten tubes, and
to contract sacs.
Smooth muscle characteristics





Sarcomeres are absent, the thick and thin filaments
are dispersed throughout the cell;
1 central nucleus
thin filaments are attached to dense bodies
(composed of -actinin)
thin filaments lack
troponin instead of it there
are two other thin filament
proteins, caldesmon
and calponin
T tubules are absent
Resting potential
from –50 to –60mV
Two broad categories of smooth muscle:


multiunit smooth muscle
and single-unit smooth muscle
(Visceral)
Multiunit smooth muscle: small, rich
innervation by ANS, little cell-cell
communication
Unitary smooth muscle (Visceral):
ANS varicosities deliver signal, gap
junctions between cells; nonneural
stimuli – most common type!
Multiunit smooth muscle




cells are isolated from one another and operate
independently
contractions of multi-unit smooth muscle are
more discrete, fine, and localized
Their contractile activity is controlled by neural
input from the autonomic nervous system
Examples of this type
of smooth muscle include:
Erector pili muscles in the skin
Ciliary muscles in the eye
Single-unit smooth muscle
(visceral; unitary)




the most common type of smooth muscle
found in: walls of vessels and hollow organs, such as
the bladder and organs of the gastrointestinal system
the individual muscle cells are connected by means of
gap junctions, which allow the passage of ions and
small molecules from one cell to the next
the muscle functions as the a single motor unit
Single-unit smooth muscle
(visceral; unitary)

Contractile activity of single unit smooth muscle is
influenced not only by the autonomic nervous
system, but also by nonneural stimuli, such as
hormones and by local tissue factors, such as
temperature, NO and pH.
estrogen and
progesterone both
increase the membrane
potential of uterus
Single-unit smooth muscle
(visceral; unitary)
The function of nerve supply is not to initiate
activity in the muscle but rather to modify it.
 NE causes relaxation of the visceral smooth
muscle (intestine, urinary bladder).
 In contrast ACh activates the muscle.
 The opposite situation exists in vascular
smooth muscles

(arterioles)
Effect of NE on
vascular
smooth muscle
Contractions:
Tonic = sustained (sphincters, bladders)
Phasic = twitchlike, produced by APs
or slow waves (intestines).
Non-electrical control: e.g., NO 
2nd mess.  intracellular Ca++ release 
contraction (endothelial cells)
Multiunit smooth muscle – nerve fibers form synapses
Single-unit (visceral) smooth muscle – nerve fibers form
varicosities; transmitter travels a longer distance
Varicosities of ANS and visceral
muscles
Distinguishing features between
skeletal and smooth muscle
Feature
Striations
Size
Skeletal muscle
Smooth muscle
Present due to transverse
register of thick and thin
filaments (Z lines line up
within the muscle fiber)
Not present since Z-line
equivalents (or dense bodies)
do not line up within the
muscle fiber
Large due to fusion of
embryonic myoblasts
Small since myoblasts do not
fuse
Shortening velocity
Fast
Slow
ATP consumption
Fast
Slow
Efficiency
High
Low
Motor end plate
Yes
No
Feature
Skeletal muscle
Smooth muscle
Second messenger
Ca2+
Ca2+ and IP3
Stimulus for Ca2+
release
Propagation of an action
potential throughout
sarcoplasmic reticulum
Neurotransmitter or hormone
activates phospholipase C in
the sarcolemma and IP3 acts
at sarcoplasmic reticulum
Ca2+ binding
Troponin
Ca-dependent myosin kinase
E-C coupling
Troponin-Ca2+ complex
causes conformational change
in the thin filament, which
allows cross bridge
Ca2+-dependent myosin
kinase phosphorylates cross
bridges, allowing attachment
to thin filament
Ca2+ re-uptake by active
transport into sarcoplasmic
reticulum and dissociation of
troponin-Ca2+ complex
Ca2+ re-uptake by active
transport into sarcoplasmic
reticulum or out of the cell and
dissociation of Ca2+dependent myosin kinase and
dephosphorylation of cross
bridges
Relaxation
Potential to divide
Lost
Maintained
Comparison of muscle types
Muscle type
Role of Ca2+
Source of Ca2+
Mechanism of
Ca2+ mobilization
Regulation of
force
Skeletal
Initiates contraction
by binding to
troponin
Intracellular from SR.
Enough Ca2+ is released to
activate all muscle protein
Depolarization of
T-tubule
Summation,
recruitment, and
preload are
varied to vary
force
Cardiac
Initiates contraction
by binding to
troponin
Intracellular from SR.
Extracellular
Amount of Ca2+ released can
be varied to vary contractile
force.
Ca2+-induced Ca2+
release
Contractility and
preload are
varied to vary
force; variations
in contractility
affect speed of
contraction.
Smooth
Activates
calmodulin, which
in turn activates
MLCK
Intracellular from SR.
Extracellular.
IP3 increases
release of Ca2+ ;
protein kinase A
increases release
of Ca2+ by SR
Recruitment,
summation,
preload, and
contractility are
varied to vary
force.
Questions
Relaxation of skeletal muscle is
associated with
a.
rapid dissociation of thick
filaments into myosin dimers
b.
uncoupling of the T-tubules
from the surface membrane
c.
reduction of intracellular Ca
ions by uptake into the SR
d.
inhibition of creatine kinase
e.
formation of "rigor" links
During a single crossbridge cycle,
a.
troponin is cleaved from
tropomyosin
b.
Ca ion dissociates from
myosin, eliciting a change in
conformation to that of rigor
link
c.
The hydrolysis of ATP on the
myosin crossbridge is the
force-generating step
d.
One ATP molecule is
hydrolized
e.
C and D

C. Relaxation is
associated with lowering
the intracellular Ca2+
concentration by the SR
to the point where Ca2+
dissociates from troponin
and there is subsequent
restoration of the inhibition
of tropomyosin on actinmyosin interaction.

E. ATP plays two
roles: it dissociates
the actin-myosin
complex, and its
hydrolysis provides
the energy for
contraction;
however, only one
ATP per crossbridge
cycle is hydrolyzed
If muscular disorder is characterized
by low level activity of glycogen
phosphorylase, an enzyme which
is rate limiting for glycolysis,
which of the following symptoms
would be characteristic of this
condition?
a.
moderate muscular activity would
be normal, but intensive muscle
activity would be disabling
b.
muscles would contract
spontaneously and irregulary
c.
contraction would be normal, but
relaxation would be impaired
d.
there would be pronounced
atrophy in all muscle fibers
e.
there would be insensivity to
normal Ca ions levels

A. Oxidative
metabolism can sustain
sufficient levels of ATP
for moderate muscle
activity. High levels of
activity, however, would
quickly exhaust the
available
phosphocreatine stores
and normally depend on
the glycolysis pathway
to furnish ATP relatively
rapidly. An increase in
muscle lactate is a
consequence of heavy
activity
In comparison to fast-twitch (type
IIB, FG) fibers, slow-twitch
(type I, SO) fibers have:
a.
a higher myoglobin content
b.
a higher glycolytic capacity
c.
more T-tubule-sarcoplasmic
reticulum junctional surface
area
d.
similar myosin isoforms
e.
different force-length
relationship
Based on the sliding filament
theory, which of the following
changes would you expect in
the sarcomere during
contraction?
a.
the length of A and H zones
should increase
b.
the length of A zone should
increase
c.
the length of H and I zones
should decrease
d.
the length of H zone should
increase
e.
the length of I zone should
decrease


A. Slow-twitch fibers are
more oxidative, with higher
levels of myoglobin to
facilitate diffusion of
oxygen. They are slower,
and this is paralleled by the
decreased T-tubulesarcoplasmic reticulum
junctional surface area,
which reflects slower
speeds of activation and
relaxation
C. Based on the sliding
filament theory and
knowledge of the structure
of sarcomeres, one can
predict that the length of A
zone depends only on the
length of thick filaments,
which remains constant
during contraction. The
length of Z and I zones, on
the other hand, depends on
the degree of thick and thin
filament overlap, and would
therefore decrease during
contraction
Ca2+
a.
b.
c.
d.
channel blockers would
have a significant effect on
muscle function in:
skeletal muscle
smooth muscle
both
neither
Ca2+binding proteins are
involved in excitation
contraction coupling in:
a.
skeletal muscle
b.
smooth muscle
c.
both
d.
neither


B. Only smooth
muscle depends on
iflux of extracellular
Ca2+ through Ca2+
channels in the cell
membrane for
excitation contraction
coupling

C. Both smooth and skeletal
muscle contain Ca2+-binding
proteins that play an
important role in E-C
coupling. In skeletal muscle,
the binding of Ca2+ by
troponin brings about
conformational changes that
ultimately result in the
availability of binding sites on
action for interaction with
myosin.
In smooth muscle, binding of
Ca2+ by calmodulin
ultimately results in
enhanced ATPase activity of
myosin globular heads.
If you were developing a drug to
treat the muscle spasticity of
several neurologic diseases
such as cerebral palsy or
multiple sclerosis, which of the
following would be most
useful?
a.
a drug that inhibited Ca2+
ATPase enzymes in the
sarcoplasmic reticulum
b.
a drug that inhibited Ca2+
channels in the cell membrane
c.
a drug that inhibited Ca2+
release from sarcoplasmic
reticulum
d.
a drug that inhibited protein
kinases
The synaptic channels on the
end-plate of skeletal muscle
are:
a.
highly selective for Na+
b.
opened when the cell
membrane depolarizes
c.
activated by acetylocholine
(Ach)
d.
inhibited by atropine
e.
responsible for the relative
refractory period

C. Inhibition of Ca2+ release
from the sarcoplasmic reticulum
would be expected to decrease
spasticity in skeletal muscle.
Smooth muscle function would
be much less influenced by this
drug because the endoplasmic
reticulum Ca2+ stores play less
of a role in smooth muscle than
in skeletal muscle. Inhibiting the
Ca2+ ATPase in sarcoplasmic
reticulum would result in
increased intracellular Ca2+. The
other agents would not be as
selective in inhibiting Ca2+
release from the sarcoplasmic
reticulum.

C. Acetylocholine (Ach) is
released from the alpha
motoneuron nerve termianl and
activates the synaptic channels on
skeletal muscle end-plate. These
channels, unlike the channels that
produce the action potential, are
not affected by changes in the
membrane potential. The Ach
receptor is inhibited by curare;
atropine blocks Ach receptors
activated by postganglionic
parasymathetic neurons. The
channel opened by the Ach
receptor is equally permeable to
Na+ and K+.
Which one of the following
proteins is important for
skeletal muscle contraction
but not for smooth muscle
contraction?
a.
Actin
b.
Myosin
c.
Troponin
d.
Myosin-adenosine
triphosphatase (ATPase)
e.
Ca2+-ATPase
Increasing the afterload on
skeletal muscle fiber
a.
increases velocity of
shortening
b.
decreases the force
produced by the muscle
during shortening
c.
decreases the interval
between excitation and
shortening
d.
increases the amount of
shortening
e.
none of above


C. In skeletal muscle,
contraction is initiated
when Ca2+ binds to
troponin. Smooth muscle
contraction is initiated by
the phosphorylation of the
myosin light-chain
proteins. Both smooth and
skeletal muscle rely on
actin, myosin, and myosinATPase for cross-bridge
cycling and on Ca2+ATPase for Ca2+
resequestration
E. The afterload is the weight
that the muscle lifts during an
isotonic contraction. When the
afterload on an isotonically
contracting skeletal muscle is
increased, the velocity of
shortening slows, the amount of
force produced by the muscle
increases (because force must
equal load for the muscle to
shorten), the interval between
excitation and shortening
increases (because it takes
longer for the muscle to build up
enough force to lift the load),
and the amount of shortening
decreases