HDE 101: Muscle Physiology 1- Anatomy and Contraction

Muscle Function

Move us, stuff, stuff through us, prevent movement

Muscle Body Composition

• Skeletal muscle - 30-40% of body weight

• Cardiac & Smooth muscle - 10% of body weight

Muscle Types

• Skeletal Muscle

  • Multi-nucleated, voluntarily contracted , striated

• Cardiac Muscle

  • Lots of lymphocytes , Intercalated Disk’s, Striated, Nucleus, Automatically controlled

• Smooth Muscle

  • No striations, nuclei and muscle cells, Automatically controlled

Skeletal Muscle Structure

Whole muscle (cm)

• Fascicle (mm)

  • Muscle Fiber (μm x 100

    • Myofibril (μm)

      • Sarcomere (μm)

        • Thick filament (nm)

        • Thin filament (nm)

Z-line

Thin filaments are joined at the Z-line

Sarcomere

Functional unit of sliding shortening

• Sliding filaments

• Composed of Thick filaments (μm) and Thin filaments (μm)

Thin Filaments (Regulatory)

• Helical actin molecules

  • Myosin binding sites

• Tropomyosin — thread like protein

  • Covers myosin binding sites

• Troponin

  • Releases tropomyosin when Ca²⁺ is bound

Thick Filaments (Motor)

• Myosin molecules - 2 golf club-shaped subunits

• Tails aligned toward middle

• Globular heads protrude out at regular intervals

  • Actin binding sites

  • ATP binding sites

Sarcomeric Structure

• Z-line

  • Defines the border of the sarcomere

  • Thin filaments joined

I-Band

• Only thin (actin) filaments , light-colored region

A-Band

• Entire length of thick (myosin) filaments, including where they overlap with thin filaments

H-Zone

• Containing only thick (myosin) filaments w/ no overlapping actin

M-Line

• Dark line running down exact center of H-zone/sarcomere, where myomesin/other proteins anchor the thick filaments

Z-line

• Defines the border of the sarcomere

• Thin filaments joined

I-Band (Isotropic Band)

• Only thin (actin) filaments , light-colored region

A-Band (Anisotropic Band)

• Entire length of thick (myosin) filaments, including where they overlap with thin filaments

H-Zone

• Containing only thick (myosin) filaments w/ no overlapping actin

M-Line

• Dark line running down exact center of H-zone/sarcomere, where myomesin/other proteins anchor the thick filaments

What would cross-section look like at Z-Line?

Z-line included only thin filaments, shouldn’t include any thick filaments

• Should have interconnections since thin filaments join at Z-line

Skeletal Muscle Fibers

• Packed with myofibrils

• Multinucleated → support many nuclei processes that req. protein

• Many mitochondria → ATP production req. energy

• Transverse Tubules

  • Extension of membrane through the cell → Allow ATP to propagate

• Specialized organelles

  • Sarcolemma = Plasma membrane

  • Sarcoplasm = Cytoplasm

  • Sarcoplasmic Reticulum = Endoplasmic Reticulum

Skeletal Muscle Fibers- Specialized Organelles

• Sarcolemma = Plasma membrane

• Sarcoplasm = Cytoplasm

• Sarcoplasmic Reticulum = Endoplasmic Reticulum

Motor Units

Motor unit

• A single motor neuron and all of the muscle fibers it innervates

  • A muscle fiber is only innervated by ONE motor unit → “1 motor unit innervates 100 muscle fibers”

Motor units are intercalated within healthy muscle

Motor neurons determine muscle contraction

Motor Unit Size

Variable

• Some <10 fibers

• Some <1000 fibers

Amount of motor units activated are key to determining how much force the muscle will make

Neuromuscular Junction

Specialized synapse that transfers an AP in a nerve to a muscle fiber

Steps of AP in a nerve to a muscle fiber

1. Motor neuron action potential

2. Ca²⁺ enters voltage-gated channels

3. Acetylcholine release

4. Acetycholine binding opens ion channels

5. Na⁺ entry

6. Local current between depolarized end plate and adjacent muscle plasma membrane

7. Muscle fiber AP initiation

8. Propagated AP in muscle plasma membrane

9. Acetylcholine degradation

How does Botox stop muscle activity?

Prevents Acetylcholine (ACh) from being released into synaptic cleft

Myasthenia Gravis

Autoimmune disorder where antibodies mediate destruction of the acetylocholine receptor →There will be less Acetylcholine receptors

Which therapies could you imagine be used in myasthenia gravis?

Prevent re-uptake/degradation of Acetylcholine

• Keep Acetylcholine in cleft longer by preventing acetylcholine esterase (enzyme) in using an inhibitor

Excitation-Contraction Coupling

1. AP propagated throughout muscle fibers by T-tubules

2. DHP receptors sense voltage change → Open ryanodine receptor coupled to it on the sarcoplasmic reticulum (SR) leading to Ca2⁺ release

   1. SR has a really high Ca²⁺ conc. , once activated it releases them

3. Cytosolic Ca²⁺ binds to troponin → removes blocking action of tropomyosin→ exposes myosin binding site

4. Myosin cross-bridges cycle to generate force using ATP

5. Cystolic Ca²⁺ pumped back into Sarcoplasmic Reticulum (SR) through SERCA pumps using ATP

6. Low cystolic Ca²⁺ leads to Ca²⁺ removal from troponin → restores tropomyosin blocking action on myosin binding site

Simple Term for Excitation-Contraction Coupling

1. AP propagated along muscle fibers through T-tubules

2. DHP receptors sense voltage change → open ryanodine receptor →Ca²⁺ released from Sarcoplasmic Reticulum (SR)

3. Ca²⁺ binding to troponin removes blocking action of tropomyosin

4. Myosin cross-bridges bind and generate force using ATP

5. Ca²⁺ transported back into SR using ATP

6. Ca²⁺ removal from troponin restores tropomyosin blocking action

Excitation-Contraction Coupling

• Ca²⁺ activates thin filament

  • Ca²⁺ binds to troponin

  • Troponin moves from inhibitor state

  • Tropomyosin slides off the actin binding site

  • Myosin cross-bridge can now bind

Excitation-Contraction Coupling - Low cytosolic Ca²⁺, relaxed muscle

• Ca²⁺ doesn’t bind to troponin → doesn’t remove blocking action of tropomyosin → Energized cross-bridge cannot bind to actin

Excitation-Contraction Coupling - High cytosolic Ca²⁺, activated muscle

• Ca²⁺ binds to troponin → troponin removes blocking action of tropomyosin → Myelin cross-bridge binding sites are exposed → Cross-bridge binds to actin and generates force

Which doesn’t change length during a shortening contraction?

A-band

• A-band is where we have thick myosin filaments → Myosin filaments don’t shorten or change size

• Areas defined by a lack of filament get smaller, but areas defined by the length of a filament won’t change

Which does change length during a shortening contraction?

I-Zone

• Region containing only thin actin filaments shortens

H-Zone

• Shorten and completely disappear during muscle contraction

Sarcomere length

• Overall distance between Z-lines decreases

Latent Period

Latent Period (lag phase) in muscle contraction. The arrival of an electrical stimulus (AP) at the muscle fiber and start of a muscle contraction has about 1 to 10 millisecond delay bc of the excitation-contraction coupling at the NMJ.