Title: Muscles
Teacher: Magdalena Gibas MD PhD
Coll. Anatomicum, 6 Święcicki Street, Dept. of Physiology
Muscles
I. The structural and functional organization of muscles
A. Functions of muscles include: movement, stability, communication (facilitate speech,
writing), control of body openings and passages, and heat production.
B. Skeletal muscle
Skeletal muscle is voluntary striated muscle usually attached to bone. It exhibits striations,
reflecting the overlapping nature of the internal contractile proteins. I band consists of thin
filaments only, A band contains thick and thin filaments, M line is composed of myosin tails
(thick filaments), Sarcomere, which is a functional unit, is located between two Z lines (Z line
– site of fixation of thin filaments). Cyclic “rowing” of thick filaments over thin shortens Iband, H zone, but A band is constant.
The series-elastic components of muscular tissue include the stretched endomysium,
perimysium, epimysium, fascia, and tendon, all of which are not excitable but do stretch and
recoil.
II. Functional structure of skeletal muscle cell
A. The muscle fiber (muscle cell)
1. Myofilaments
Myofilaments are central to muscle contraction. Three kinds exist: thick filaments, thin
filaments, and elastic filaments.
2. Sarcomere
Sarcomere is the unit of contraction of a muscle fiber.
3.Sarcoplasmic reticulum (SR)
Sarcoplasmic reticulum is a reservoir for calcium ions, it joins with T tubules to form terminal
cisternae
III. The nerve-muscle relationship
A. Motor neurons
1. Skeletal muscle is innervated by somatic motor neurons whose cell bodies are in the
brainstem and spinal cord. The axons of motor neurons are called somatic motor fibers. Each
muscle fiber (of skeletal muscle) is supplied by only one motor neuron.
B. The motor unit
A motor unit consists of one nerve fiber and all the muscle fibers it innervates. It behaves as a
single functional unit and contracts as one. Multiple motor units within a muscle are able to
"work in shifts."
C. The neuromuscular junction
1. A nervous impulse traveling down the neuron triggers the release of neurotransmitter
(acetylcholine - ACh) from synaptic vesicles into synaptic cleft. ACh binds to receptors,
which are present in the motor end plate (part of sarcolemma = membrane of muscle fiber).
This is the signal for depolarization of motor end plate. An enzyme called
Acetylcholinesterase breaks down Ach after its diffusion from Ach receptor.
IV. Behavior of skeletal muscle fibers
A. Resting potential of cell membrane (sarcolemma) is negative, about - 80 to - 90mV.
B. Excitation-contraction coupling
During excitation-contraction coupling, action potentials in the muscle fiber lead to activation
of the myofilaments. The wave of action potential (AP) reaches the T tubules and continues
into terminal cisternae of SR. AP affect dihydropyridine receptors (DHPR) in the T
tubules. It activates ryanodine receptors on SR and opens calcium channels of SR
(ryanodine receptors work as a calcium channels). Calcium ions are released then into the
cytosol. Calcium ions bind to the troponin of the thin myofilaments, causing the troponintropomyosin complex to shift aside, exposing the active sites on the actin filament. The heads
of the myosin filaments (called crossbridges) can now bind to these active sites and initiate
contraction.
B. Contraction
During the contraction phase, sliding of the thin myofilaments across the thick ones causes
the muscle fiber to shorten. The sliding filament theory of Hanson and Huxley suggests that
thin filaments slide over thick ones, causing sarcomeres to shorten. The head of each myosin
molecule contains myosin ATPase that releases energy from ATP. In preparation for action,
the myosin binds and hydrolyzes an ATP molecule, and is now in the "cocked" position.
When the active sites on the actin filament are exposed, the myosin head contacts the active
site, releases energy, and performs a power stroke (movement). At the end of a power stroke,
myosin binds to a new ATP, releases the actin, and returns to its original position in a
recovery state. The cycle of power stroke and recovery is repeated many times during muscle
contraction.
C. Relaxation
When nervous stimulation ceases, the muscle relaxes. Acetylcholinesterase breaks down ACh
so the muscle stops generating its action potentials. Calcium is carried back to the
sarcoplasmic reticulum by active transport (it requires ATP break down).
D. The length -tension relationship and tonus
1. The degree of actin and myosin overlap determines tension development by contracting
muscle. If the muscle is already contracted, stimulation will cause a weak contraction.
Conversely, if the muscle is overstretched, little overlap exists between actin and myosin
filaments, and contraction can damage the muscle.
V. Behavior of whole skeletal muscles
A. Threshold, latent period, twitch
1. Muscle have a threshold or minimal voltage, necessary to produce a muscle contraction.
2. If a muscle is given a single, brief stimulation, it will show a quick cycle of contraction and
relaxation called a twitch.
3. A very brief latent period exists between two successive twitches in which the muscle
cannot contract.
B. Contraction strength of twitches
1. The strength of contraction of a whole muscle is increased as more motor units are
activated.
2. Another way to produce a stronger muscle contraction is to stimulate the muscle at a higher
frequency.
3. Muscle cells exhibit treppe, or the “staircase phenomenon”, in response to a series of
stimuli of the same strength. This is probably due to the inability of the muscle cells to fully
return calcium to the sarcoplasmic reticulum during a shot period between stimulations.
4. After a twitch, a short refractory period exists during which the muscle cannot respond to
another stimulus.
5. If a second stimulation arrives before the end of the refractory period, the muscle will
achieve temporal summation (or wave summation) and achieve a higher level of tension.
6. If the stimuli are frequent enough that the muscle cannot relax completely in between, a
state of incomplete tetanus is reached. If there is no time to relax at all between stimuli,
complete tetanus is achieved.
C. Isometric and isotonic contraction
1. Isometric contraction is tensing of the muscles without a change in length. If two ends of a
muscle are fixed such that it cannot shorten, and the muscle is stimulated to contract, tension
develops in the muscle, but the length of a muscle does not change.
2. Isotonic contraction is contraction with a change in muscle length but no change in tension.
VI. Skeletal muscle metabolism
A. ATP sources
1. During exercise, muscles use energy produced by aerobic respiration (when there is an
adequate supply of oxygen) and anaerobic fermentation (when oxygen is limited, and lactic
acid accumulates).
2. For immediate energy, muscle tissue relies on the phosphagen system to supply ATP.
3. For short-term energy, after the phosphagen system is exhausted, muscles reply temporarily
on the glycogen-lactic acid system for ATP
4. For long-term energy, the respiratory and cardiovascular systems catch up and deliver
enough oxygen to meet the demands of aerobic respiration.
B. Slow- and fast-twitch fibers
1. Slow-twitch fibers (red) – aerobic metabolism (using oxygen; fatigue resistent).
2. Fast-twitch fibers (white) – anaerobic metabolism (no oxygen; low endurance)
3. Although both slow and fast fibers are present in most muscles of the body, one or the other
usually predominates.
VII. Smooth muscle
1. Smooth muscle is composed of spindle – shaped myocytes, they contain only one nucleus,
and no visible striations or sarcomeres.
2. There are no Z lines in smooth muscle, but its thin filaments attach to so called dense
bodies. Smooth muscles lack T tubules of cellular membrane.
3. Calcium enters through channels in the sarcolemma.
4. Most calcium for smooth muscle contraction comes from the extracellular fluid, not the
sarcoplasmic reticulum, and it binds to calmodulin, not to troponin.
5. The two functional categories of smooth muscle are multiunit and single-unit.
6. Partly because of its latch-bridge mechanism, smooth muscle can remain partially
contracted for a prolonged period without additional nervous stimulation. This ability, plus its
fatigue-resistance, enables smooth muscle to maintain smooth muscle tone.
7. The ability of an organ such as the stomach or urinary bladder to expand results partly from
the stress-relaxation response of smooth muscle.
VIII. Cardiac muscle
A. Composition.
1. Single nucleus; fibers are smaller than in skeletal muscle.
2. T tubule – larger than in skeletal muscle and is located at the Z line rather than at the
junction of A and I bands.
B. Excitation - contraction coupling
1. Ca2+ induced Ca2+ release. Ca2+ release from SR is triggered by Ca2+, not by membrane
depolarization!!!
a. The T tbubule DHP receptor in cardiac muscle, unlike the DHPR in skeletal muscle,
contains Ca2+ channel (or works as a Ca2+ channel), through which Ca2+ enters the cell
during the action potential. See appropriate picture from the book.
b. The SR RYR (ryanodine receptor) is opened by the influx of Ca2+ from the T tubule. Now
compare it with skeletal muscle! See appropriate picture (book).
2. The amount of Ca2+ release is under physiologic control:
a. The amount of Ca2+ entering the cell and within SR may be increased by catecholamines
b. the amount of intracellular Ca2+ is regulated by the Na+-Ca2+ exchanger, an antiport
mechanism driven by the Na+ gradient that transports one Ca2+ out of the cell for every 3
Na+ molecules that enter
3. Great amount of Ca2+ for heart contraction comes from T tubules, thus concentration in
ECF (extracellular fluid) greatly influences strength of contraction
C. Shortening and force development
1. Summation and tetanus are not possible (Cardiac cells have long AP and long twitches and
do not show temporal summation)
2. The sarcomere length before contraction (the preload) depends on how much blood has
entered the heart.
3. The force of contraction can vary at a given sarcomere length if the amount of Ca2+
entering the cell is changed. This is under physiologic control and, thus, is an important
regulator of cardiac muscle contractile force.
IX. Comparison of cardiac, skeletal, and smooth muscle
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 through DHP
receptor (L type) Ca2+
channels. 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 through
voltage- and receptoractivated Ca2+ channels.
IP3 increases
release of Ca2+ ;
protein kinase A
increases release
of Ca2+ by SR
Recruitment,
summation,
preload, and
contractility are
varied to vary
force.
Formation of
latch-bridges
reduces speed
of contractility.