Quiz 2

Functions of skeletal muscles

• Produce body movements

• Stabilize body position against gravity

• Regulate organ volume

• Move fluids and solid food and wastes in the body

• Produce heat

Skeletal muscles

• Muscles of skeleton (attached to bones)

• Diaphragm

• Parts of esophagus and eye

• External anal sphincter

• Voluntary and reflex control

Properties of muscle tissue

• Electrical excitability

• Contractility

• Extensibility

• Elasticity

Muscle fiber

• Cellular unit of skeletal muscle

• Each fiber contains thousands of tubular structures called myofibrils (highly organized contractile proteins)

• Fibers bound together in fasciculi

Parts of the skeletal muscle organization

Myofilaments (actin & myosin) → myofibrils → muscle fibers → fascicles → skeletal muscle

Sarcomeres

Contractile apparatus of SKM made up of thick (myosin) + thin (actin) myofilaments arranged in interdigitating arrays

Contractile proteins associated with muscle fiber

• Actin

• Myosin

Regulatory proteins associated with muscle fiber

Help form myosin-actin cross bridges

• Troponin

• Tropomyosin

Structural proteins associated with muscle fiber

• Titin

• Dystrophin

• Myomesin

• Nebulin

NMJ

Specialized chemical synapse that links motor nerve impulses to release acetylcholine onto nicotinic receptors which initiate SKM activation

Myofilaments of SKM

• Myosin is assembled into thick filaments → S2 region of the molecule is flexible & tail region is stiff

• Actin-binding sites are located on globular myosin heads, which also contain light chains with ATPase activity

• Thin (actin) filaments are formed from G-actin monomers into helical F-actin strands → associated with troponin-tropomyosin complex to form the functional actin filament

Muscle contraction of SKM

1. Nerve impulse arrives at end of motor nerve axon (somatic nerves) causing Acetylcholine(ACh) release into synapse via exocytosis

2. ACh floods across synaptic gap and attaches to receptors on sarcolemma

3. Permeability of sarcolemma changes and Na+ enters cell

4. Muscle impulse (AP) is triggered

5. Muscle impulse travels via transverse tubules (T-tubules) throughout muscle cell = T-tubule depolarization

6. Ca2+ diffuses from SR into myoplasm → binds to troponin on actin

7. Myosin heads binds to actin forming cross bridges

8. Cross-bridges pull thin filament (power stroke), ADP and P released from myosin

9. New ATP binds to myosin, releasing linkages

10. ATP splits which provides power to “cock” the myosin cross-bridges

SKM Excitation

1. Nerve impulse arrives at axon terminal

2. Triggers release of Ach by exocytosis

3. ACh diffuses across synaptic cleft

4. ACh binds to receptors on muscle motor end plate

5. Sarcolemma becomes more permeable to Na+

6. Na+ triggers release of muscle action potential

7. Muscle action potential travels along outside of sarcolemma and into T-tubules

8. APtriggers Ca++ release from SR

9. Ca++ binds to troponin on thin filament → releases allosteric inhibition of tropomyosin on actin

10. Tropomyosin is pulled aside, revealing binding sites

11. Myosin links to & pulls actin to contract muscle

SKM Relaxation

1. Acetylcholinesterase decomposes ACh in synapse

2. Action potential (impulse) ends

3. SR actively pumps Ca++ back into SR

4. Tropomyosin moves back to cover binding sites

5. Myosin heads detach

6. Muscle fiber returns to its longer resting length

SKM cross-bridge cycle

• Produces force and shortens sarcomere

• Requires ATP and is activated by increase in intracellular Ca2+

Interdigitation

• Trigerred and controlled by the entrance of Ca2+ ion into a protein called troponin located on actin filament

• When Ca2+ exits, bridges are uncoupled → relaxing the filaments which lengthen

• ↑ Ca2+ → ↑ muscle contraction

• ↓ Ca2+ → ↓ muscle contraction

• Too much Ca2+ → muscle fails

Motor unit summation

• Summed force: Total force generated in whole SKM due to activation of both motor units to produce a stronger muscle contraction

• Total force: simple spatial summation of twitches from two motor units

• First, a brief partial tetanus is created in the first motor unit (temporal summation) → additional motor units are recruited, increasing muscle force

Regulating contractile force of SKM

• Varying the number of motor units stimulated (spatial summation)

• By increasing the frequency of activation by motor neurons (temporal summation)

  • Temporal summation can summate force and produce tetany

Twitches

Brief, singles contractions of muscle fibers in response to a single stimulus

Smooth muscle

• Myogenic contractions: can both contract and relax actively on its own via ANS unlike SKM

• Contraction and relaxation can be tonic, graded or phasic and is controlled by direct chemical and physical stimuli, as well as receptor-mediated activation by neurotransmitters, hormones or chemical ligands

• Relaxtion is active and not just the absence of contraction → associated with lowering cytoplasmic Ca2+

• Exhibit single or summed twitch contractions

• Produce graded responses in form of smooth increments in contraction or relaxation rather than the “all-or-off” characteristic of SKM

• No visible striations

• Contain thick and thin filaments but different than SKM

• Fewer myosin filaments than SKM → slower contraction and greater economy of energy usage (begins to contract 50-100ms after being excited and remains contracted for 1-3 sec) & longer contraction (30 times longer than single SKM contraction)

• Can maintain same tension of contraction as SKM at less than 1% of energy cost

• Visceral SM: can be physically and electrically coupled allowing activation to spread from cell-to-cell

• Vascular SM: contains more multiunit type SM that are innervated cell by cell

Smooth Muscle myofilament organization

• 1:16 ratio of thick to thin filaments (1:2 ratio in SKM)

• Tropomyosin associated w/ thin filaments but no troponin present

• No sarcomeres - thick and thin filaments are collected into budles that correspond to myofibrils

• Contain non-contractile intermediate filaments that attach to dark-staining dense bodies that are distributed throughout the cell and occasionally anchored to the sarcolemma

Dense bodies

• Serve as attachment points for thin filaments of SM

• Counterparts of Z lines in SKM

• Intermediate filament-dense body network forms strong, cable-like intracellular cytoskeleton → harnesses pull generated by sliding of SM myofilaments during contraction

Smooth muscle sheets

• At least 2 SM sheets are present and oriented at right angle to each other

• Longitudinal layer runs with long axis of organ

• Circular layer runs around circumference of organ

• Cyclic contraction and relaxation of these layers allows lumen of organ to alternately constrict and dilate for peristalsis

• Contraction of SM in rectum, urinary bladder and uterus helps those organs to expel their contents

Where is SM found?

• GI tract

• Bladder

• Blood vessels

• Uterus

• Tracts of respiratory, urinary and reproductive system

• Eyes (iris)

• Skin (erect hair)

SM innervation

• Lacks highly structured NMJ of SKM

• Instead, innervating nerve fibers approach SM fibers → release Nts into synaptic cleft of SM cells via bulbous endings called varicosities

Contraction of SM

• Adjacent SM cells exhibit slow, synchronized contractions

• Whole sheet responds to stimulus in unison → reflects electrical coupling of SM cells by gap junctions

  • Whereas SKM cells are electrically isolated from one another (each stimulated to contract by its own NMJ)

• Gap junctions coordinate changes in membrane potential and intracellular Ca2+ between adjacent SM cells

• Ca2+ binds to thick filaments rather than thin filaments as in SKM

• Myosin ATP-ase activity is 1/10th that in SKM, even in optimal conditions

Pacemaker cells

• Specialized SM cells

• Act as “drummers” once excited, to set contractile pace for entire sheet of SM

• Self-excitatory membranes → can depolarize spontaneously in absence of external stimuli

• However, both rate and intensity of SM contraction may be modified by neural and chemical stimuli

Mechanism of contraction in SM

1. Actin and myosin interact by sliding filament mechanism

2. Rise intracellular Ca2+ ion levels (final trigger for contraction)

3. Sliding process is energized by ATP

Reaction pathways in regulation of cross-bridge cycle in SM

1. Activation begins when cytoplasmic Ca2+ levels are increased and Ca2+ binds to calmodulin → activates myosin light-chain kinase

2. The kinase catalyzes phosphorylation of light chain in myosin head, changing it to an active form

3. Phosphorylated myosin head increases affinity for active sites actin (thin filaments) → cross-bridge cycling → initiates contraction but at slower rate than SKM

4. When Ca2+ levels reduce, it leaves calmodulin → kinase is inactivated → myosin light-chain phosphatase dephosphorylates myosin, inactivating it

5. Cross-bridge cycle stops and muscle relaxes

SM tone

• Ability of SM to maintain tension for a prolonged period while using relatively small amounts of ATP (important to overall body homeostasis)

• Small arterioles and over visceral organs are routinely called on to maintain a moderate degree of contraction (without fatiguing)

• Since energy requirements of SM are low, it can generate adequate ATP to support its contractile activity even in absence of O2 → occurs via anaerobic pathways

SM regulation of contraction

• AP generated by binding of neurotransmitter molecules to membrane receptors → release of Ca2+ ions into sarcoplasm

• Not all neural signals result in SM activation and not all SM activation is result of neural signals

  • Can generate their own AP by influx of Ca2+ ions

Source of cytosolic Ca2+ ions in SM cells

• Extracellular space through voltage-gated calcium channels and

• Intracellularly via release from sarcoplasmic reticulum