MUSCLE PHYSIOLOGY

3 types of muscles

  • Skeletal muscle

    • Multiple nuclei in a single cell

    • Skeletal muscle cell = muscle fiber

  • Cardiac muscla

    • Intercalated disc

  • Smooth muscle

Skeletal muscle

  • Half of the body's mass is composed of skeletal muscle

  • Most skeletal muscles linked to bones by tendons

  • Forces and movements developed during contractions are transmitted to the skeleton

    • Frontalis

    • Deltoid

    • Biceps

    • Pectoralis

    • Quadriceps

    • Tibialis

  • Composed of muscle fibers(cells), connective tissue, blood vessels and nerve

    • Muscle fibers are long and multinucleated

    • Striated, voluntary (conscious control)

    • Nuclei are peripherally located

    • Develop from myoblasts

      • Numbers remain constant

1. Connective Tissue Sheath

  • Epimysium: dense regular connective tissue surrounding entire muscle

  • Perimysium: collagen and elastic fibers, surrounding a fascicle (contain blood vessel and nerves)

    • Fascicle: a group of muscle fibers.

  • Endomysium: loose connective tissue surrounding individual muscle fibers.

2. Microanatomy of Skeletal Muscle

  • Sarcolemma: cell membrane, forms T tubules which project into cell

  • Myofibrils (specialized organelles): made of protein filaments. 2 main types: myosin and actin filaments

  • Sarcomere: contractile unit of muscle

  • Sarcoplasmic reticule (SR): specialized smooth ER

    • Stores calcium and releases it on demand

Myosin filaments

  • Thick filaments (16 nm)

  • Single filament contains roughly 300 myosin molecules

  • Myosin heads from cross bridges (link thick and thin filaments together during contraction)

    • Contain ATPase enzymes (split ATP)

Actin filaments

  • Has a myosin binding site (cross bridge binding site)

  • Tropomyosin prevent binding of myosin heads to actin when cell at rest

  • Troponin holds tropomyosin in place, has Ca2+ binding site

    • Anchored to the Z disc

Sarcomere

  • The smallest contractile unit of a myofibril

  • About 10000 sarcomere per myofibril, end to end

  • Composed of thick filament, thin filament and Z lines

    • M line: protein to which myosin attach

    • Z line: attachment for actin filaments

    • A band: dark band

    • I band: light band

    • H zone: only myosin

Cross-bridge formation

Properties of Skeletal Muscle

  • Excitability/responsiveness: Receive and respond to stimuli

  • Contractility: Ability to shorten (forcibly) when adequately stimulated

  • Extensibility: Muscle cells can be stretched

  • Elasticity: Ability to recoil and resume their resting length after being stretched

  • Nerve stimulus and action potential

For contraction to occur, a skeletal muscle must

  • Be stimulated by a motor neuron to contract

  • Propagate an electrical current, or action potential, along its sarcolemma

  • Have a rise in intracellular Ca2+ levels, the final stimulus for contraction

Motor unit – one motor neuron and all the muscle fibers it activates

  • One motor neuron can stimulate a few muscle cells or hundreds of them

  • Muscles that control fine movements have small motor units

  • Large weight-bearing muscles have large motor units.

Neuromuscular Junction: Region where the motor neuron stimulates the muscles

  • Axon of neuron branches into axon terminals

  • Neuromuscular junctions: contain vesicle filled with neurotransmitters

  • Neurotransmitter that stimulate skeletal muscle cells (acetylcholine)

  • Synaptic cleft: gap between axon terminal and sarcolemma of muscle cell, filled with interstitial fluid.

Troponin complex

  • Low cytosolic Ca2+: energized cross-bridge cannot bind to actin > relaxed muscle

  • High cytosolic Ca2+: cross-bridge binding sites are exposed > cross-bridge binds to actin and generates force > activated muscle

MECHANISM OF MUSCLE CONTRACTION

The sliding filament theory

  • Activation by nerve causes myosin heads (cross bridges) to attach to binding sites on the thin filament

  • Myosin heads then bind to the next site of the thin filament and pull them toward the center of the sarcomere

  • This continued action causes a sliding of the myosin along the actin

  • The result is that muscle is shortened (contracted)

Muscle response

  • “All or none” principle: Minimal stimulus needed to cause contraction

  • Force of skeletal muscle contraction can be changed by

    • Motor unit summation

    • Tetanic contraction

    • Length-tension relationship

    • Muscle force depends upon the number of fibers stimulated

      • More fibers contracting results in greater muscle tension

    • Muscles can continue to contract unless they run out energy

Graded muscle responses

  • Twitch: single, brief contraction. Not a normal muscle function

  • Tetanus (summing of contraction): One contraction is immediately followed by another

    • The muscle does not completely return to a resting state

    • The effect are added

  • Unfused (incomplete) tetanus: Some relaxation occurs between contractions

    • The results are summed

  • Fused (complete) tetanus: No evidence of relaxation before the following contractions.

    • The result is a sustained muscle contraction

Types of muscle contraction

  • Isotonic: Force remained constant throughout the shortening period

  • Isometric: muscle stays the same length during contraction

  • Concentric: the muscle shortens when performing an action

  • Eccentric: the muscle lengthens under tension

Energy for Muscle contraction

  • Muscle used stored ATP for energy

  • ATP bonds are broken to release energy

  • Three pathways for ATP regeneration

    • Direct phosphorylation of ADP by creative phosphate

    • Aerobic respiration

    • Anaerobic glycolysis and lactic acid formation

      • Only 25% of energy is used – rest relapsed as heat

Type of muscle fibers

  • Type 1: Slow oxidative (SO)

    • Small, contract slowly (low ATPase activity)

    • Use oxidative phosphorylation (aerobic)

    • Eg: soleus muscle in the leg

  • Type 2A: Fast oxidative

    • Medium sized, contract quickly (lots of force)

      • Mostly oxidative phosphorylation

  • Type 2B: Fast glycolytic

    • Large (more myofilaments), contract quickly

    • Use anaerobic glycolysis

Muscle fatigue and oxygen deficit

Muscle fatigue: unable to contract even with a stimulus

  • Common cause for muscle fatigue is oxygen debt

  • Oxygen deficit occurs after prolonged muscle activity, causing fatigue

  • Oxygen must be repaid to tissue to remove oxygen deficit

  • Increasing acidity (lactic acid) and lack of ATP cause the muscle contract less

  • Work that a muscle can do and how long without fatigue depends on blood supply

  • Without adequate oxygen, lactic acid accumulates and ATP supply under low which leads to fatigue

Effect of Excise on Muscles

  • Exercise increases muscle size, strengths and endurance

  • Aerobic (endurance), exercise (biking, jogging) results in stronger, more flexible muscles with greater resistance to fatigue

  • Makes body metabolism more efficient

  • Improves digestion, coordination

  • Resistance (isometric) exercises (weight lifting) increases muscles size and strength

Muscles and Body movements

  • Movement is attained due to a muscle moving an attached bone

  • Muscles are attached to at least two points

    • Origin: attachment to an immovable or less bone

    • Insertion: attachment to a moveable bone

Types of Ordinary Body Movements

  • Flexion

    • Decreases the angle of the joint

    • Brings two bones closer together

    • Typical of hinge joints like knee and elbow

  • Extension

    • Opposite of flexion

    • Increases angle between two bones

  • Rotation: Movement of a bone around its longitudinal axis

    • Common in ball and socket joints

  • Abduction: Movement of a limb away from the midline

  • Adduction

    • Opposite of abduction

    • Movement of a limb toward the midline

  • Circumduction

    • Combination of flexion, extension, abduction and adduction

    • Common in ball and socket joints

Smooth muscle

Key differences from skeletal muscle

  • No myofibrils or sarcomere (no striations)

  • No t-tubules

  • Tropomyosin does not block binding sites

  • No troponin but instead Calmodulin protein regulates smooth

muscle contraction

  • Contraction is initiated by a Ca-regulated phosphorylation of myosin

  • Contract in all dimensions

b. Multi-unit Smooth Muscle

  • Unorganized cells that contract as individual cells

  • Function as separate units

    • E.g: the iris of the eye, piloerector muscle, wall of large blood vessels.

  • Single-unit Smooth muscle

    • Form sheets of muscle

  • Cells are connected by gap junctions

  • A large number of cells respond as a single unit

  • Muscle fibers contract as a group

    • E.g: Visceral organs

  • Self-excitable (does not require nervous stimulation for contraction) – myogenic

    • Fibers become excited and contract as a single unit

    • Cells electrically linked by gap junctions

    • Contraction is slow and energy-efficient (well suited for hollow organs)

Smooth muscle contraction mechanism

  • Ca2+ enters mostly from ECF (voltage-gated Ca2+ channels)

  • Ca2 induced Ca2 released:

  • Ca2+ acts as second messenger, activating myosin kinase, which phosphorylates myosin

  • Cross bridge cycling occurs until Ca2+ no longer available ( actively pumped back to ECF and SR)

Innervation of Smooth Muscle

  • Innervated by autonomic nerve system

  • Lacks neuromuscular junctions

  • Innervating nerves form varicosities

  • Varicosities release neurotransmitters into synaptic clefts called

diffuse junctions

Smooth muscle regulation

  • Neurotransmitters are acetylcholine and norepinephrine

  • Hormones important as epinephrine and oxytocin

  • Neighboring cells can activates smooth contraction via gap junction

  • Some visceral muscle exhibits autorhythmic contractions ( spontaneous active pacemaker cell)

  • Tends to contract in response to sudden stretch but no to slow increase in length

  • Exhibits relatively constant tension: Smooth muscle tone

Norepinephrine & Epinephrine:

  • Depending on the type of receptors

    • Epinephrine bound to beta-adrenergic receptors on smooth muscle cells of the intestine causes them to relaxation

    • Epinephrine also binds to the alpha2-adrenergic receptor found on smooth muscle cells lining the blood vessels in the intestinal tract, skin, and kidneys causes the arteries to contraction (constriction).

    • Norepinephrine causes constriction of the smooth muscle in juxtaglomerular apparatus in the kidneys, leading to an inhibited flow to nephron

Nitroglycerine

  • Nitroglycerine is converted to NO, which relaxes blood vessels