Exam 2

PNB Module 3-4

What 4 key things do muscles have?

• Excitability

• Contractility

• Extensibility

• Elasticity

Excitability

Ability of muscle tissue to respond to stimuli (e.g., action potentials).

Contractility

The capability of muscle fibers to shorten when stimulated.

Elasticity

Tendency of a muscle to return to its original shape after contraction.

Extensibility

Ability of muscle tissue to stretch beyond normal length depending on its situation.

Components of a muscle belly

• Fascicles

• Muscle Cells( Fibers)

• Myofibrils

• Myofilaments

Fascicles

Bundles of muscle fibers that make up the muscle belly, surrounded by perimysium.

Perimysium

The connective tissue that surrounds fascicles within a muscle, providing support and protection.

Muscle Fibers

Individual long cylindrical cells containing multiple nuclei; are full of myofibrils.

Myofibrils

Cylindrical bundles of filamentous contractile proteins( myofilaments) (e.g., myosin and actin), synonymous with "muscle cell".

Myofilaments

Individual protein bundles within myofibrils (double-helical actin thin filament and myosin thick filament).

Sarcolemma

The cell membrane surrounding a muscle fiber, providing structural support and playing a role in muscle contraction.

T-Tubules(Transverse Tubules)

Extensions of the sarcolemma; rich with leak K+ and voltage-gated N+ & K+ & channels, and DHP receptors (DHPRs); allow for action potentials to propagate throughout the fiber.

Sarcoplasmic Reticulum (SR)

Specialized smooth endoplasmic reticulum that stores calcium ions; features extensive terminal cisternae surrounding T-tubules in a "triad" arrangement.

Sarcoplasm

Muscle fiber cytoplasm rich in organelles (e.g., mitochondria and glycogen granules).

Sarcomere

Defined by the area between two adjacent Z-discs, acts as the functional contractile unit

M-line

Center of the A-band, anchoring thick filaments.

H-zone

Center of the A-band where only thick filaments(myosin) are present.

Thick filaments

Composed of myosin with its own fast endogenous ATPase activity to grant spring potential energy.

thin filaments

Composed of actin (double-helical), troponin C, and tropomyosin.

Accessory Proteins

titin (elastic, anchors myosin to Z-discs), nebulin (aligns the actin double helix thin filaments), and CapZ (holds actin to Z-discs).

titin

A large protein that functions as a molecular spring, providing elasticity and stability to muscle fibers by anchoring myosin filaments to Z-discs.

Nebulin

a giant protein in skeletal muscle, acting as a molecular ruler to set thin filament length and regulate muscle contraction by interacting with actin

CapZ

a capping protein that caps the barbed end of actin filaments in muscle cells.

I-band

Region containing only thin filaments(actin), bisected by the Z-disc

A-band

region corresponding to the length of the thick filaments.

Z-discs

Anchor thin filaments and mark the boundaries of a sarcomere.

Motor unit

single motor neuron and the muscle fibers it controls. usually contains just a few muscle fibers in an entire muscle. a muscle may have many motor units.

Larger muscles have

more motor units than smaller muscles

Muscle Fibers & All or None Principle

Each muscle fiber obeys the all or none principle. Either the whole muscle fiber contracts, or not at all.

Henneman’s Size Principle

As force increases, more and more motor units are recruited to generate larger force

S-Type/ Slow-oxidative fibers (Slow Twitch)

Fatigue resistant, high endurance, easily excitable.

Fast-fatigue resistant fibers (Fast Twitch)

Bigger, Average excitability; resistant to fatigue, helps you maintain an action.

Fast-fatigable fibers (Fast Twitch)

Very big, low excitability. Not recruited unless needed. High power output but fatigue quickly

Order of muscle fiber recruitment

1. S-Type/ Slow-oxidative fibers (Slow Twitch)

2. Fast Fatigue Resistant fibers (fast twitch)\

3. Fast Fatigable fibers (fast twitch)

Why do fast-fatigable fibers fatigue quickly?

Few mitochondria, Anaerobic metabolism → less ATP available, low levels of myoglobin (that stores O2.)

Which fiber can be found in dark meat?

S-Type/ Slow-oxidative fibers (Mitochondria makes it dark)

Only muscles activated by the _______ neuron will activate

same

Weak contraction (in terms of units)

Small # of motor units

Strong contractions(in terms of units)

Large # of motor units

neuromuscular junction

The synapse between a motor neuron(pre synaptic) and a muscle fiber (post synaptic).

Synaptic Knob

Expanded end of the neuron containing vesicles.

Synaptic Vesicles

Membrane-bound sacs filled with acetylcholine (ACh)

Synaptic Cleft

Narrow gap between the synaptic knob and the motor end plate.

Motor End Plate

Region of the sarcolemma that contains folds and indentations to increase surface area, enhancing receptor availability.

ACh Receptors

Nicotinic ACh receptors located in the motor end plate; bind ACh to initiate muscle contraction.

Acetylcholinesterase (AChE)

Enzyme that breaks down ACh quickly to terminate the signal.

Motor Neuron - Pre-synaptic Events

1. Action Potential (AP) arrives at the pre-synaptic terminal.

2. Depolarization triggers activation of voltage-gated Ca2+ channel.  Ca2+ ions rush into the pre-synaptic terminal.

3. Ca²+ influx causes synaptic vesicles to fuse with the pre-synaptic membrane (exocytosis), releasing ACh into the synaptic cleft.

4. Ach diffuses across the synaptic cleft, 2 each binding to Ach Receptors

5. Channels (which are the same as the receptors) open.

6. Sodium ions enter muscle fiber, potassium ecits. Membrane potential becomes less negative- depolarizes.

7. Once Vm reaches threshold, action potential propagates along the sarcolemma.

All 5 steps of vesicle release:

• Docking: The synaptic vesicle, filled with neurotransmitters, physically attaches to the presynaptic membrane via the interaction of Rab GTPases on the vesicle with their effectors on the target membrane.

• Priming: The SNARE complex, consisting of synaptobrevin, syntaxin, and SNAP-25, then assembles, pulling the vesicle close to the membrane and preparing it for a rapid merger.

• Fusion: Upon receiving a calcium signal sensed by synaptotagmin, the SNARE complex undergoes a conformational change that drives the complete merger of the vesicle's membrane with the presynaptic membrane.

• Release: This fusion event opens a pore, releasing the vesicle's neurotransmitter contents into the synaptic cleft.

• Recycling: The protein clathrin coats the patch of vesicle membrane, causing it to bud inward and pinch off via the action of dynamin, reforming a new vesicle that can be refilled with neurotransmitters.

ACh Action in Synaptic Cleft

1. ACh Diffusion: ACh diffuses across the synaptic cleft.

2. Ach Binding: Two ACh molecules bind to each nicotinic ACh receptor on the motor end plate.

DHP(dihydropyridine receptors)

a modified Ca2+ channel receptor; voltage centers of t-tubules in muscles

Ryanodine Receptors(RYR)

Mechanical Calcium release channels in the sarcoplasmic reticulum that are activated by dihydropyridine receptors (DHP) and play a key role in muscle contraction.

Post-synaptic Events & Excitation(Potential)-Contraction(Action) (Ca2+ )Coupling

1. Somatic motor neuron releases ACh at neuromuscular junction.

2. Net entry of Na+ through ACh receptor-channel initiates a muscle action potential

3. Action potential in t-tubule alters conformation of DHP receptor.

4. Ca2+ binds to troponin, allowing actin-myosin binding

5. Myosin (motor protein) heads execute power stroke, pulling the actin filaments toward the center of the sarcomere

6. Actin filament slides toward center of sarcomere bc of pulling.

Calcium center in neurons

synaptotagmin 1,

Calcium center in muscles

troponin

Myasthenia Gravis

An autoimmune disorder characterized by muscle weakness, especially in the face and throat, resulting from antibodies blocking or destroying nicotinic ACh receptors at the motor end plate.

TTX (Tetrodotoxin)

Blocks voltage-gated Na⁺ channels, preventing nerve and muscle action potentials.

BoTox (Botulinum Toxin)

Prevents the release of ACh from pre-synaptic terminals, leading to muscle paralysis

The H-zone has_____

Myosin without actin

The I-band has____

actin without myosin

During muscle contraction what happens to the A-band

Doesn’t change its length due to overlapping of myosin and actin filaments.

Structure of Thin filaments

5-6 nm in diameter Double helix of two strands of bead shaped actin molecules twisted around each other

G-actin

the globular, monomers form of actin that polymerizes to form filaments

F actin

the filamentous form of actin that is composed of polymerized G-actin monomers.

Tropomyosin

a protein that binds to actin filaments and helps regulate muscle contraction by blocking myosin binding sites.

Troponin C

it initiates a conformational change that causes tropomyosin to shift, thereby exposing the myosin-binding sites on the actin filaments

Sliding Filament Theory

Describes the process of muscle contraction by which thin (actin) filaments slide over thick (myosin) filaments, shortening the sarcomere.

The response in the Sliding Filament Theory

Contraction

Cross Bridge Cycle

1. Calcium Ion Release & Troponin-Tropomyosin Shift: Increased cytosolic Ca²⁺ ions, released from the SR, bind to troponin C, which then shifts tropomyosin , exposing myosin-binding sites on actin.

2. Myosin Binding to Actin (Cocked State) A "cocked" myosin head (energized by ATP hydrolysis) binds to the actin active site.

3. Phosphate Ejection: Inorganic phosphate () is ejected from the myosin head, strengthening the cross-bridge bond.

4. Power Stroke: The spring-loaded myosin-head pivots, undergoes a conformational change, pulling the actin filament toward the M-line (center of the sarcomere);

5. ADP is ejected.

6. ATP Binding & Myosin Release : A new ATP molecule binds to myosin, causing it to detach from actin (no MLC in skeletal muscle).

7. ATP Hydrolysis & Resetting: The myosin head's endogenous ATPase activity hydrolyzes ATP to ADP and, re-cocking and spring-loading the myosin heavy chain head, preparing for another cycle.

Why is Ca2+ important in the contraction?

Binds to troponin, exposes the binding site.

Molecular Basis of Muscle Contraction

1. Ca²+ levels increase in cytosol

2. Ca²+ binds to troponin

3. Troponin-Ca²+ complex pulls tropomyosin away from actin’s myosin-binding site.

4. Myosin binds strongly to actin and completes power stroke.

5. Actin filament moves.

Cardiac Muscle

• Organized similarly to skeletal muscle, with sarcomeres and striations

• smaller than skeletal muscle cells, featuring branching.

• Contains intercalated discs, gap junctions, desmosomes

• No direct innervation of most of the muscle cells; exhibits automaticity.

Contraction Mechanism of Cardiac Muscle

identical to that of skeletal muscle, relying on the sliding filament theory and cross-bridge cycling activated by

binding to troponin C.

Cardiac APs

Cardiac APs feature a long plateau phase with high levels of Ca²+ influx through voltage-gated channels (VGCCs).

Smooth Muscle

• Non-striated muscle, involuntary control, and mostly found in hollow organs (e.g., intestines, blood vessels).

• Contractile filaments are organized differently than in striated muscle; they are anchored to dense bodies (analogous to Z-discs).

Contraction Mechanism of Smooth Muscle

utilizes calmodulin (CaM) instead of troponin.

Molecular components of smooth muscle contraction

• Calmodulin (CaM)

• Myosin Light Chain Kinase (MLCK):

• Myosin Light Chain Phosphatase (MLCP)

Myosin Light Chain Kinase (MLCK)

Activated by Ca2+-CaM complex; phosphorylates myosin light chain (MLC) regulatory protein.

Myosin Light Chain Phosphatase (MLCP)

Dephosphorylates MLC, leading to relaxation.

Smooth Muscle Sarcoplasmic Reticulum (SR)

• Ca²+-induced Ca²+ release at Sr RYRs

• GPCR triggered IP3 producted → IP3 Induced Ca²+ release at IP3Rs

Smooth Muscle Control and APs

Smooth muscle may be controlled by APs, graded potentials, neurotransmitters (NTs), stretch, and hormones.

Smooth muscle can undergo MANY different types of APs and rests less negative (-40mv to -50mv)

What makes the cardiac muscle different from the skeletal?

• Shorter fibers and smaller cells

• often branched w/ gap junction & desmosomes

• Uni or bi nucleate

• No direct innervation of most of the muscle cells.

Cardiac Action Potential Steps

1. Rapid depolarization due to opening of voltage-gated fast Na^{+} channels.

2. Plateau (of maintained depolarization) due to opening of voltage-gated slow Ca^{2+} channels (VGCCs) and closing of some K^{+} channels; voltage-gated K^{+} channels it remains open.

3. Repolarization due to opening of more voltage gated K^{+} channels, and blocking of Ca^{2+} channels.

What’s special about depolarization, refractory period, and contraction in cardiac myocytes?

They’re all simulataneous

Muscle tension

force created by muscle

Load

• weight (force or resistance) that opposes contraction

Single twitches

muscle relaxes completely between stimuli

Summation

Stimuli closer together do not allow muscle to relax fully

Summation leading to unfused tetanus(repetitive stimuli)

stimuli are far apart. they can relax slightly between stimuli

Summation leading to complete tetanus

muscle reaches steady tension. If muscle fatigues, tension decreases rapidly.

Tetanus

state of sustained muscle contraction resulting from rapid successive stimuli.

Fatigue

the decline in the ability of a muscle to generate force.

When do muscles fatigue?

strong stimulation keeps a muscle in a state of tetanus too long.

Isometric contraction

force without moving loadthat occurs when muscle length stays constant during tension generation.

Isotonic contraction

Create force and move load

Concentric Action

A type of isotonic contraction where the muscle shortens while generating force, typically lifting a load.

Eccentric Action

A type of isotonic contraction where the muscle lengthens while generating force, typically during the lowering phase of a load.

Series ______ elastic elements _____

shorten; stretch

Contraction Mechanics at the sarcomere

1. Muscle at rest

2. Isometric Contraction: Muscle has not shortened.

   Sarcomeres shorten, generating

   force, but elastic elements

   stretch, allowing muscle length

   to remain the same

3. Isotonic contraction: Sarcomeres shorten
   more but, because elastic
   elements are already
   stretched, the entire
   muscle must shorten

Central fatigue

decline in performance due to factors affecting the central nervous system, leading to reduced motor output.

during prolonged exercise or intense training.