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🏋️ Muscle Contraction - Complete Exam Notes

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1. STRUCTURE OF SKELETAL MUSCLE (Basis for Understanding Contraction)

Muscle Fiber

• Each muscle cell (fiber) is cylindrical, 1-4 cm long, 10-100 µ diameter
• Covered by sarcolemma (cell membrane); cytoplasm = sarcoplasm
• Contains nuclei, myofibrils, mitochondria, sarcoplasmic reticulum, Golgi apparatus, glycogen droplets

Myofibril

• Fine parallel filaments running the entire length of the fiber
• Diameter: 0.2-2 µ; made up of repeating units called sarcomeres

Sarcomere

• Definition: Structural and functional unit of skeletal muscle; basic contractile unit
• Extent: Between two 'Z' lines
• Resting length: 2-3 µ
• Contains alternating bands:
  • 'I' band (Light/isotropic): contains only actin filaments; divided by the 'Z' line
  • 'A' band (Dark/anisotropic): contains myosin (full length); actin extends into it
  • 'H' zone: light area in middle of 'A' band; contains only myosin (no actin)
  • 'M' line: in center of H zone; formed by myosin binding proteins

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2. CONTRACTILE PROTEINS

Myosin (Thick Filaments)

• Diameter: 115 Å, Length: 1.5 µ; located in 'A' band
• Each myosin filament = ~200 myosin molecules
• Each myosin molecule:
  • MW = 480,000
  • 2 heavy chains (MW 200,000 each) + 4 light chains (MW 20,000 each)
  • Tail portion: two heavy chains twisted as a double helix
  • Head portion: globular; has two attachment sites - one for actin, one for ATP
  • The head also acts as ATPase enzyme
• Projections from myosin = cross-bridges, with enlarged myosin heads at their tips

Actin (Thin Filaments)

• Diameter: 20 Å, Length: 1 µ; extends from 'Z' lines across 'I' band into 'A' band (up to 'H' zone)
• Each actin filament = 300-400 F-actin molecules (polymer of G-actin)
• F-actin arranged as a double helix
• Each F-actin molecule has an active site where myosin head binds

Tropomyosin

• 40-60 molecules per actin filament, MW = 70,000
• In the relaxed state, tropomyosin covers all active sites of F-actin → prevents myosin binding
• Lies along the double helix groove of actin

Troponin

• Three subunits:
  • Troponin I → attached to F-actin
  • Troponin T → attached to tropomyosin
  • Troponin C → binds calcium ions (the regulatory unit)

Exam key: Troponin C is the calcium sensor. When Ca²⁺ binds to it, the whole troponin-tropomyosin complex shifts, uncovering the active site on actin.

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3. SARCOTUBULAR SYSTEM

T-Tubules (Transverse Tubules)

• Formed by invagination of sarcolemma → open to exterior
• Penetrate the fiber through and through
• ECF runs through their lumen
• Function: Rapid transmission of action potential from sarcolemma to the interior of muscle fiber

L-Tubules / Sarcoplasmic Reticulum

• Closed tubules running longitudinally; surround each myofibril
• Dilate at intervals to form terminal cisternae
• T-tubule + 2 terminal cisternae = Triad (located at A-I junction in human skeletal muscle)
• Function: Store calcium ions → release Ca²⁺ upon excitation → triggers contraction

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4. MECHANISM OF MUSCLE CONTRACTION (Molecular Basis)

Step 1 - Excitation-Contraction (E-C) Coupling

1. Motor nerve impulse → travels through neuromuscular junction
2. Action potential generated in sarcolemma
3. AP spreads over sarcolemma → travels deep into fiber via T-tubules
4. AP reaches cisternae of L-tubules → cisternae are excited
5. Calcium ions (Ca²⁺) released from cisternae into sarcoplasm
6. Ca²⁺ = the coupling link between excitation and contraction

Step 2 - Role of Troponin and Tropomyosin

1. In the resting state: tropomyosin blocks active sites on F-actin → myosin cannot bind
2. Ca²⁺ released into sarcoplasm binds to Troponin C
3. Ca²⁺ binding changes the shape/position of the troponin molecule
4. Troponin pulls tropomyosin away from the active sites of actin
5. Active sites on F-actin are uncovered and exposed
6. Myosin heads immediately attach to exposed active sites

Step 3 - Sliding Mechanism (Ratchet/Walk-Along Theory)

1. Myosin head binds to the active site on F-actin (cross-bridge formation)
2. ATP attached to myosin head is cleaved by ATPase → ADP + Pi (energy released)
3. The head tilts toward the arm ("power stroke") - drags actin filament toward center of sarcomere
4. ADP and Pi are released; a new ATP molecule binds to the myosin head
5. The head detaches from actin and returns to original position
6. Head attaches to the next active site further along actin and repeats
7. This ratchet-like cycling pulls actin filaments toward the center of the sarcomere
8. The Z lines come closer → sarcomere shortens → muscle contracts

Changes in Sarcomere During Contraction

Memory tip: Only the 'A' band stays the same. Everything else shortens!

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5. MUSCLE RELAXATION

1. Stimulation stops → no more action potential
2. Ca²⁺ is actively pumped back into the L-tubules (requires ATP)
3. Ca²⁺ in sarcoplasm decreases → Ca²⁺ releases from Troponin C
4. Tropomyosin returns to cover active sites on actin
5. Myosin detaches from actin → muscle relaxes

Important: Relaxation is an active process (needs ATP to pump Ca²⁺ back). Physical relaxation appears passive, but the chemical process is active.

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6. ENERGY FOR MUSCLE CONTRACTION

Source 1 - ATP Breakdown (immediate)

• ATP → ADP + Pi + Energy
• Sufficient only for < 1 second of full contraction
• Energy used for: action potential spread, Ca²⁺ release, myosin head movement, sliding mechanism

Source 2 - Creatine Phosphate (CP) (seconds)

• Lohmann's reaction: ADP + CP → ATP + Creatine
• (Enzyme: creatine phosphotransferase)
• CP is plentiful in resting muscle; provides energy for only a few seconds

Source 3 - Carbohydrate Metabolism (sustained)

• Glycogen stored in sarcoplasm undergoes catabolism
• Glycolysis (Embden-Meyerhof pathway):
  • Glycogen → 2 pyruvic acid molecules
  • Net: 2 ATP produced
• Without O₂ (Anaerobic): Pyruvic acid → Lactic acid → Cori cycle (liver converts lactic acid back to glycogen)
• With O₂ (Aerobic): Pyruvic acid → Acetyl CoA → Krebs cycle (TCA cycle)
  • 2 ATP + 16H released per Krebs cycle

Total ATP from 1 Glycogen Molecule

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7. NEUROMUSCULAR JUNCTION (NMJ) - How the Signal Reaches the Muscle

Structure

• Junction between motor nerve terminal and muscle fiber
• Axon terminal (motor endplate): contains mitochondria + synaptic vesicles (containing acetylcholine, ACh)
• Synaptic trough/gutter: depression in the muscle fiber under the nerve terminal
• Synaptic cleft: space between presynaptic and postsynaptic membranes; contains acetylcholinesterase (AChE)
• Postsynaptic membrane: has folds (subneural clefts) and nicotinic ACh receptors

Neuromuscular Transmission (Sequence of Events)

1. Action potential reaches axon terminal
2. Opens voltage-gated Ca²⁺ channels in presynaptic membrane
3. Ca²⁺ enters → synaptic vesicles fuse with presynaptic membrane (exocytosis)
4. ACh released into synaptic cleft (~300 vesicles, ~10,000 ACh molecules per vesicle)
5. ACh binds to nicotinic receptors on postsynaptic membrane
6. Ligand-gated Na⁺ channels open → Na⁺ enters → Endplate Potential (EPP) develops (-90mV → -60mV)
7. EPP triggers action potential in muscle fiber
8. ACh destroyed by AChE within ~1 ms (prevents repeated firing)
9. Choline taken back up (reuptake) into axon terminal and recycled

Endplate Potential (EPP)

• A graded potential (not an action potential)
• Non-propagative, but triggers the action potential in the muscle fiber

Miniature Endplate Potential (MEPP)

• Caused by spontaneous release of a single quantum of ACh
• Amplitude: ~0.5 mV
• Cannot produce AP alone, but multiple MEPPs summate to form EPP

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8. ACTION POTENTIAL IN MUSCLE

Resting Membrane Potential

• Skeletal muscle: -90 mV (inside negative, outside positive = polarized state)
• Maintained by: Na⁺-K⁺ pump (3 Na⁺ out, 2 K⁺ in per cycle) + selective membrane permeability

Action Potential Phases

• Spike potential = rapid rise + rapid fall
• Total action potential: lasts ~0.4 ms (spike) + several ms afterpotentials

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9. THERMAL CHANGES DURING CONTRACTION

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10. QUICK SUMMARY TABLE - KEY NUMBERS

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EXAM-FOCUS KEY POINTS

1. Sliding filament theory: Actin slides over myosin - 'A' band length unchanged, 'I' band and 'H' zone shorten.
2. Troponin C is the Ca²⁺ receptor. Without Ca²⁺, tropomyosin blocks actin's active sites.
3. T-tubules spread the AP inward; L-tubules store and release Ca²⁺.
4. Power stroke = myosin head tilts, pulling actin. Needs ATP for detachment (not attachment).
5. E-C coupling: AP → T-tubule → cisternae → Ca²⁺ release → contraction.
6. Relaxation is active (needs ATP to pump Ca²⁺ back into L-tubules).
7. NMJ blocker types: Curare/Bungarotoxin = receptor blockers; Botulinum toxin = prevents ACh release; Succinylcholine = keeps membrane depolarized.
8. Rigor mortis: No ATP → Ca²⁺ floods in → actomyosin complex formed and locked (cannot relax). Resolves when lysosomal enzymes (cathepsins/calpains) break down the actomyosin.