Muscles and Muscle Tissue

Overview of Muscle Tissue

Muscle constitutes nearly half of the body’s mass.
It transforms chemical energy (ATP) into directed mechanical energy to exert force.
Investigation of muscle involves:
- Types of muscle tissue.
- Characteristics of muscle tissue.
- Muscle functions.

Types of Muscle Tissue

Terminology:
- Myo, mys, and sarco are prefixes for muscle.
  - Example: sarcoplasm (muscle cell cytoplasm).
Three types of muscle tissue:
- Skeletal.
- Cardiac.
- Smooth.
Only skeletal and smooth muscle cells are elongated and referred to as muscle fibers.

Skeletal Muscle

Skeletal muscle tissue is packaged into skeletal muscles: organs attached to bones and skin.
Skeletal muscle fibers are the longest and have striations (stripes).
Also called voluntary muscle: can be consciously controlled.
Contract rapidly, tire easily, powerful.
Key words: skeletal, striated, and voluntary.

Cardiac Muscle

Cardiac muscle tissue is found only in the heart.
Makes up bulk of heart walls.
Striated.
Involuntary: cannot be controlled consciously.
Contracts at a steady rate due to the heart’s own pacemaker, but the nervous system can increase the rate.
Key words: cardiac, striated, and involuntary.

Smooth Muscle

Smooth muscle tissue is found in the walls of hollow organs.
- Examples: stomach, urinary bladder, and airways.
Not striated.
Involuntary: cannot be controlled consciously.
Key words: visceral, nonstriated, and involuntary.

Characteristics of Muscle Tissue

All muscles share four main characteristics:
- Excitability (responsiveness): ability to receive and respond to stimuli.
- Contractility: ability to shorten forcibly when stimulated.
- Extensibility: ability to be stretched.
- Elasticity: ability to recoil to resting length.

Muscle Functions

Four important functions:
- Produce movement: responsible for all locomotion and manipulation.
  - Example: walking, digesting, pumping blood.
- Maintain posture and body position.
- Stabilize joints.
- Generate heat as they contract.

Skeletal Muscle Anatomy

Skeletal muscle is an organ made up of different tissues with three features: nerve and blood supply, connective tissue sheaths, and attachments.

Nerve and Blood Supply

Each muscle receives a nerve, artery, and veins.
- Consciously controlled skeletal muscle has nerves supplying every fiber to control activity.
Contracting muscle fibers require huge amounts of oxygen and nutrients.
- Also need waste products removed quickly.

Connective Tissue Sheaths

Each skeletal muscle, as well as each muscle fiber, is covered in connective tissue.
Support cells and reinforce whole muscle.
Sheaths from external to internal:
- Epimysium: dense irregular connective tissue surrounding entire muscle; may blend with fascia.
- Perimysium: fibrous connective tissue surrounding fascicles (groups of muscle fibers).
- Endomysium: fine areolar connective tissue surrounding each muscle fiber.

Attachments

Muscles span joints and attach to bones.
Muscles attach to bone in at least two places:
- Insertion: attachment to movable bone.
- Origin: attachment to immovable or less movable bone.
Attachments can be direct or indirect:
- Direct (fleshy): epimysium fused to periosteum of bone or perichondrium of cartilage.
- Indirect: connective tissue wrappings extend beyond muscle as ropelike tendon or sheetlike aponeurosis.

Muscle Fiber Microanatomy and Sliding Filament Model

Skeletal muscle fibers are long, cylindrical cells that contain multiple nuclei.
Sarcolemma: muscle fiber plasma membrane.
Sarcoplasm: muscle fiber cytoplasm.
Contains many glycosomes for glycogen storage, as well as myoglobin for $O_2$ storage.
Modified organelles:
- Myofibrils.
- Sarcoplasmic reticulum.
- T tubules.

Myofibrils

Myofibrils are densely packed, rodlike elements.
- Single muscle fiber can contain 1000s.
- Accounts for ~80% of muscle cell volume.
Myofibril features:
- Striations.
- Sarcomeres.
- Myofilaments.
- Molecular composition of myofilaments.

Striations

Stripes formed from repeating series of dark and light bands along the length of each myofibril.
- A bands: dark regions.
  - H zone: lighter region in the middle of the dark A band.
    - M line: line of protein (myomesin) that bisects the H zone vertically.
- I bands: lighter regions.
  - Z disc (line): coin-shaped sheet of proteins on the midline of the light I band.

Sarcomere

Smallest contractile unit (functional unit) of muscle fiber.
Contains A band with half of an I band at each end.
- Consists of the area between Z discs.
Individual sarcomeres align end to end along the myofibril, like boxcars of a train.

Myofilaments

Orderly arrangement of actin and myosin myofilaments within the sarcomere.
- Actin myofilaments: thin filaments.
  - Extend across the I band and partway into the A band.
  - Anchored to Z discs.
- Myosin myofilaments: thick filaments.
  - Extend the length of the A band.
  - Connected at the M line.
The sarcomere cross section shows a hexagonal arrangement of one thick filament surrounded by six thin filaments.

Molecular Composition of Myofilaments

Thick filaments: composed of protein myosin that contains two heavy and four light polypeptide chains.
- Heavy chains intertwine to form the myosin tail.
- Light chains form the myosin globular head.
During contraction, heads link thick and thin filaments together, forming cross bridges.
Myosins are offset from each other, resulting in a staggered array of heads at different points along the thick filament.
Thin filaments: composed of fibrous protein actin.
- Actin is a polypeptide made up of kidney-shaped G actin (globular) subunits.
  - G actin subunits bear active sites for myosin head attachment during contraction.
  - G actin subunits link together to form long, fibrous F actin (filamentous).
  - Two F actin strands twist together to form a thin filament.
- Tropomyosin and troponin: regulatory proteins bound to actin.
Other proteins help form the structure of the myofibril.
- Elastic filament: composed of protein titin.
  - Holds thick filaments in place; helps recoil after stretch; resists excessive stretching.
- Dystrophin
  - Links thin filaments to proteins of the sarcolemma.
- Nebulin, myomesin, C proteins bind filaments or sarcomeres together.
  - Maintain alignment of sarcomere.

Clinical - Homeostatic Imbalance 9.1

Duchenne Muscular Dystrophy (DMD) is the most common and serious form of muscular dystrophies, muscle-destroying diseases that generally appear during childhood.
Inherited as a sex-linked recessive disease, so almost exclusively in males (1 in 3600 births).
Appears between 2 and 7 years old when the boy becomes clumsy and falls frequently.
The disease progresses from extremities upward, finally affecting head, chest muscles, and cardiac muscle.
With supportive care, people with DMD can live into their 30s and beyond.
Caused by a defective gene for dystrophin, a protein that links thin filaments to the extracellular matrix and helps stabilize the sarcolemma.
The sarcolemma of DMD patients tears easily, allowing entry of excess calcium, which damages contractile fibers.
Inflammation follows, and regenerative capacity is lost, resulting in increased apoptosis of muscle cells and a drop in muscle mass.

Sarcoplasmic Reticulum and T Tubules

Sarcoplasmic reticulum: a network of smooth endoplasmic reticulum tubules surrounding each myofibril.
- Most run longitudinally.
- Terminal cisterns form perpendicular cross channels at the A–I band junction.
- SR functions in the regulation of intracellular $Ca^{2+}$ levels.
- Stores and releases $Ca^{2+}$ .
T tubules
- Tube formed by protrusion of sarcolemma deep into cell interior.
  - Increases muscle fiber’s surface area greatly.
  - Lumen is continuous with extracellular space.
  - Allows electrical nerve transmissions to reach deep into the interior of each muscle fiber.
- Tubules penetrate the cell’s interior at each A–I band junction between terminal cisterns.
  - Triad: area formed from the terminal cistern of one sarcomere, T tubule, and terminal cistern of neighboring sarcomere.

Triad Relationships

T tubule contains integral membrane proteins that protrude into the intermembrane space (space between tubule and muscle fiber sarcolemma).
- Tubule proteins act as voltage sensors that change shape in response to an electrical current.
SR cistern membranes also have integral membrane proteins that protrude into the intermembrane space.
- SR integral proteins control the opening of calcium channels in SR cisterns.
When an electrical impulse passes by, T tubule proteins change shape, causing SR proteins to change shape, causing the release of calcium into the cytoplasm.

Sliding Filament Model of Contraction

Contraction: the activation of cross bridges to generate force.
Shortening occurs when tension generated by cross bridges on thin filaments exceeds forces opposing shortening.
Contraction ends when cross bridges become inactive.
In the relaxed state, thin and thick filaments overlap only slightly at the ends of the A band.
The sliding filament model of contraction states that during contraction, thin filaments slide past thick filaments, causing actin and myosin to overlap more.
- Neither thick nor thin filaments change length, just overlap more.
When the nervous system stimulates a muscle fiber, myosin heads are allowed to bind to actin, forming cross bridges, which cause the sliding (contraction) process to begin.
Cross bridge attachments form and break several times, each time pulling thin filaments a little closer toward the center of the sarcomere in a ratcheting action.
- Causes shortening of the muscle fiber.
- Z discs are pulled toward the M line.
- I bands shorten.
- Z discs become closer.
- H zones disappear.
- A bands move closer to each other.

Muscle Fiber Contraction

Background and Overview

The decision to move is activated by the brain, and the signal is transmitted down the spinal cord to motor neurons, which then activate muscle fibers.
Neurons and muscle cells are excitable cells capable of action potentials.
- Excitable cells are capable of changing resting membrane potential voltages.
AP crosses from neuron to muscle cell via the neurotransmitter acetylcholine (ACh).
Ion Channels
- Play the major role in changing membrane potentials.
- Two classes of ion channels:
  - Chemically gated ion channels – opened by chemical messengers such as neurotransmitters
    - Example: ACh receptors on muscle cells
  - Voltage-gated ion channels – open or close in response to voltage changes in membrane potential
Anatomy of Motor Neurons and the Neuromuscular Junction
- Skeletal muscles are stimulated by somatic motor neurons.
- Axons (long, threadlike extensions of motor neurons) travel from the central nervous system to skeletal muscle.
- Each axon divides into many branches as it enters the muscle.
- Axon branches end on muscle fiber, forming the neuromuscular junction or motor end plate
  - Each muscle fiber has one neuromuscular junction with one motor neuron.
- Axon terminal (end of axon) and muscle fiber are separated by a gel-filled space called the synaptic cleft.
- Stored within axon terminals are membrane-bound synaptic vesicles
  - Synaptic vesicles contain the neurotransmitter acetylcholine (ACh).
- Infoldings of the sarcolemma, called junctional folds, contain millions of ACh receptors.
- NMJ consists of axon terminals, synaptic cleft, and junctional folds.
The Big Picture - Four steps must occur for skeletal muscle to contract:
- Events at the neuromuscular junction
- Muscle fiber excitation
- Excitation-contraction coupling
- Cross bridge cycling

Events at the Neuromuscular Junction

AP arrives at the axon terminal.
Voltage-gated calcium channels open, calcium enters the motor neuron.
Calcium entry causes the release of the ACh neurotransmitter into the synaptic cleft.
ACh diffuses across to ACh receptors ( $Na^+$ chemical gates) on the sarcolemma.
ACh binding to receptors opens gates, allowing $Na^+$ to enter, resulting in an end plate potential.
Acetylcholinesterase degrades ACh.

Clinical - Homeostatic Imbalance 9.2

Many toxins, drugs, and diseases interfere with events at the neuromuscular junction.
- Example: myasthenia gravis: a disease characterized by drooping upper eyelids, difficulty swallowing and talking, and generalized muscle weakness.
  - Involves shortage of Ach receptors because a person’s ACh receptors are attacked by their own antibodies.
  - Suggests this is an autoimmune disease.

Generation of an Action Potential Across the Sarcolemma

The resting sarcolemma is polarized, meaning a voltage exists across the membrane.
- The inside of the cell is negative compared to the outside.
The action potential is caused by changes in electrical charges.
Occurs in three steps:
- Generation of end plate potential.
- Depolarization.
- Repolarization.

End Plate Potential

ACh released from the motor neuron binds to ACh receptors on the sarcolemma.
Causes chemically gated ion channels (ligands) on the sarcolemma to open.
$Na^+$ diffuses into the muscle fiber.
- Some $K^+$ diffuses outward, but not much.
Because $Na^+$ diffuses in, the interior of the sarcolemma becomes less negative (more positive).
Results in local depolarization called end plate potential.

Depolarization

Generation and propagation of an action potential (AP).
If the end plate potential causes enough change in membrane voltage to reach a critical level called the threshold, voltage-gated $Na^+$ channels in the membrane will open.
The large influx of $Na^+$ through channels into the cell triggers the AP that is unstoppable and will lead to muscle fiber contraction.
The AP spreads across the sarcolemma from one voltage-gated $Na^+$ channel to the next one in adjacent areas, causing that area to depolarize.

Repolarization

Restoration of resting conditions.
$Na^+$ voltage-gated channels close, and voltage-gated $K^+$ channels open.
$K^+$ efflux out of the cell rapidly brings the cell back to its initial resting membrane voltage.
Refractory period: the muscle fiber cannot be stimulated for a specific amount of time until repolarization is complete.
Ionic conditions of the resting state are restored by the $Na^+-K^+$ pump.
- $Na^+$ that came into the cell is pumped back out, and $K^+$ that flowed outside is pumped back into the cell.

Excitation-Contraction (E-C) Coupling

Excitation-contraction (E-C) coupling: events that transmit the AP along the sarcolemma (excitation) are coupled to the sliding of myofilaments (contraction).
The AP is propagated along the sarcolemma and down into the T tubules, where voltage-sensitive proteins in tubules stimulate $Ca^{2+}$ release from the SR.
- $Ca^{2+}$ release leads to contraction.
The AP is brief and ends before contraction is seen.

Muscle Fiber Contraction: Cross Bridge Cycling

At low intracellular $Ca^{2+}$ concentration:
- Tropomyosin blocks active sites on actin.
- Myosin heads cannot attach to actin.
- The muscle fiber remains relaxed.
Voltage-sensitive proteins in T tubules change shape, causing the sarcoplasmic reticulum (SR) to release $Ca^{2+}$ to the cytosol.
At higher intracellular $Ca^{2+}$ concentrations, $Ca^{2+}$ binds to troponin.
Troponin changes shape and moves tropomyosin away from myosin-binding sites.
Myosin heads are then allowed to bind to actin, forming a cross bridge.
Cycling is initiated, causing sarcomere shortening and muscle contraction.
When nervous stimulation ceases, $Ca^{2+}$ is pumped back into the SR, and contraction ends.

Four Steps of the Cross Bridge Cycle

Cross bridge formation: the high-energy myosin head attaches to the actin thin filament active site.
Working (power) stroke: the myosin head pivots and pulls the thin filament toward the M line.
Cross bridge detachment: ATP attaches to the myosin head, causing the cross bridge to detach.
Cocking of the myosin head: energy from the hydrolysis of ATP “cocks” the myosin head into a high-energy state.
- This energy will be used for the power stroke in the next cross bridge cycle.

Clinical - Homeostatic Imbalance 9.3

Rigor mortis
- 3–4 hours after death, muscles begin to stiffen.
  - Peak rigidity occurs about 12 hours postmortem.
- Intracellular calcium levels increase because ATP is no longer being synthesized, so calcium cannot be pumped back into the SR.
  - Results in cross bridge formation.
- ATP is also needed for cross bridge detachment.
  - Results in myosin head staying bound to actin, causing a constant state of contraction.
- Muscles stay contracted until muscle proteins break down, causing myosin to release.