lecture 12

Skeletal muscle organization

wrapped in Connective Tissue Sheaths
• Support and reinforce the whole muscle as a unit
• Three concentric layers
connected to bone by tendon

Wrapped in Fascia
• Deep fascia: Separates individual muscles
• Superficial: Separates muscles from skin

3 layers

Epimysium: surrounds the whole muscle
• Perimysium: surrounds bundles of muscle fibers
• Surrounded unit called a fascicle
• Endomysium: surrounds the individual muscle fiber

Microanatomy of skeletal muscle

-Sarcolemma: plasma membrane of the muscle fiber
- Sarcoplasm: cytoplasm of the muscle cell
Sarcomere
• Functional unit of the muscle

Z disks (cytoskeletal disc that interconnects the actin filaments)

muscle length increases

adding more sarcomeres not by increasing the length of the sarcomere

Transverse tubules (T-tubules)

• Membranous tubes that travel perpendicular to the length of the fiber
• Allow for the conduction of an action potential from the surface of the cell through

Sarcoplasmic reticulum (SR)

• Modified endoplasmic reticulum, surrounds each myofibril like a mesh sleeve
• Storage for high [Ca2+] that when released facilitate a muscle contraction

Terminal Cisternae

• Blind ended sacs at the end of the SR adjacent to T-tubules
• Serve as the reservoir for [Ca2+]

neuromuscular junction

exictation of skeletal muscle cell
1. calcium entry at synaptic knob
2. release of ach
3. ach diffuses and binds to ach receptor

I band

portion of the thin filaments only

A band

region of thick filaments and the overlapping thin filament

H band

consists of thick filaments only

Z band

transverse proteins that interconnect the thick filaments,

molecules of sacromere

-Titin
• Single-stranded elastic protein
• Acts as a spring to passively recoil the muscle cell to its resting length after a stretch
• Stabilize the position of the thick filament relative to the thin filament

- Nebulin
• Inelastic protein that helps align actin filaments

- a actinin
• Crosslinks antiparallel thin filaments

thin filaments

actin
• Backbone
• Possess functional binding sites for myosin

Tropomyosin
• Long chain that binds to actin and “hides” the myosin binding site

Troponin
• 3 functional units
• TnI binds actin and inhibits contraction
• TnT binds Tropomyosin
• TnC binds Ca2+

thick filaments

• Myosin2 protein oriented in opposing directions with the heads facing outward

• Myosin heavy chain (globular head and long tail)
• Essential myosin light chain (MLC-1 or ELC)
• Regulatory light chain (MLC-2 or RLC)

• Heavy chain globular heads possess
• Actin-binding site
• ATPase site

• MLCs related to CaM superfamily
• Bind to and stabilize neck region
• Light and heavy chains vary for muscle class

calcium

key to crossbridging

powerstroke

atp binds to head, atp hydrolis, confromationa chnage in mysoin head

relaxation

Extrusion occurs by way of pumps (PMCA) and exchangers (NCX)
• SR has pump (SERCA) which actively pumps Ca2+ from the cytosol into the SR
• Ca2+ is sequestered in SR

Condition of no Action Potential
• No Ca2+ release
• Ca2+ pumped out of cytosol
• Actin and myosin can not interact

types of contraction

1. Isotonic – muscle tension (force generated) remains constant as muscle length changes

2.Isometric – muscle doesn’t change length, so tension develops at constant muscle length

isotonic

muscle tension (force generated) remains constant as muscle length changes

Concentric – muscle is shortening with tension
Eccentric – muscle is lengthening with tension

freq summation

• A twitch is a single contraction in a muscle fiber

Temporal summation of twitches produces an additive tension in the fiber

• Tetanus is a smooth, sustained contraction at maximal strength resulting from rapid successive action potential
• Individual twitches are no longer distinguishable
• Insufficient time between stimulations to return Ca2+ back to SR

motor unit

A single motor neuron and the muscle fibers it controls
• The number of fibers in a motor unit varies
• Dependent on the type of action performed by that muscle

• Delicate activity: few muscle fibers
• Coarse activity: many muscle fibers

• Fibers in a motor unit are not clustered but dispersed throughout a muscle
• A stimulation of a motor unit will result in an evenly distributed contraction (twitch)

Multiple-fiber summation

• Addition of motor neuron pools to increase tension
• Ensures constant force over time

fast vs slow muscle fiber

Fast have higher ATPase activity (quicker tension development), conduct action potentials faster, & pump Ca2+ into SR faster

• Fast are more powerful, are quicker to produce a twitch and twitch lasts a shorter duration

oxidative v. glycolytic:

• Reliance on oxidative phosphorylation vs glycolysis for ATP.

• Oxidative phosphorylation yields more ATP and thus fatigues slower than glycolysis.

• Glycolytic fibers are said to be fatigable.

Slow oxidative (type I) – red muscle

– red muscle
-Slow and less powerful contractions
• Smallest muscle cell
• Large amounts of myoglobin

fast oxidative (type IIa) – red muscle

– red muscle
• Least numerous

Fast glycolytic (type IIb) – white

• Most prevalent
• Largest in diameter
• Significantly less myoglobin

cardiac muscle

Uninucleate and smaller than skeletal muscle
• Branched & connected to one another via intercalated discs

some of the cardiac muscle generate self-induced APs which is spread to the other cells within the syncytium (pacemaker cells)

• T-tubules are larger than those found in skeletal muscle

• Smaller sarcoplasmic reticulum

• Relies on extracellular Ca2+ to release the sequestered Ca2+ (CICR)

• ~1/3rd the volume of a cardiac muscle cell are mitochondria

Smooth muscle contractions

multiunit smooth muscle
• Made up of discrete motor units that function independently of one another
• Have neuromuscular junctions

Single unit smooth muscle
• gap junctions
• Contract as a single coordinated unit
• Self-excitable: resting potential fluctuates without influence from external forces resulting in spontaneous depolarization

slow wave potential

fire when threshold is reached

Gradual alternating hyperpolarizations & depolarizations
• If threshold is reached, burst of action potentials

pacemaker poteintial

depolarize to threshold
Slow depolarization resulting in an action potential

smooth muscle

No sarcomeres, but have dense bodies scattered throughout the cell body

Two molecules inhibit actin myosin activity
• Calponin binds actin and tropomysoin and prevents MHC ATPase activity
• Caldesmon appears to block actin myosin interaction

• Dense bodies = contain the same protein as Z lines, held into place by intermediate filaments

smooth muscle contractions

depends on calcium
uses signaling pathway via CaM
• Ca2+ binds to and activates CaM