Week 9 ELM 18: Muscle I

Skeletal Muscle Structure

Classification of Muscle

• Skeletal, cardiac, and smooth muscle are the three types of muscle.
• Skeletal muscle is striated.

The Real Reason For Brains

• Brains are primarily for controlling muscles.

Skeletal Muscle Structure

• Components include:
  • Bone
  • Tendon
  • Epimysium
  • Perimysium
  • Blood vessel
  • Muscle fiber
  • Fascicle
  • Endomysium
• Fascicle: Latin for "bundle," signifying "strength through unity".

Skeletal Muscle Fibre

• Key components:
  • Sarcolemma
  • Nucleus
  • Mitochondria
  • Myofibrils
  • T tubule
  • Terminal cisterna
  • Triad
  • Sarcoplasmic reticulum

The Sarcomere

Sarcomere Structure

• Key components:
  • Sarcomere
  • H-Zone
  • A-band
  • I-band
  • Z-line
  • M-line

Striations

• Sarcomere structure gives rise to striations in skeletal muscle.
• A-band, Z-line, M-line, I Band, H Zone, I Band are responsible to the striations.

Sarcomere Length and Force of Contraction

• Optimum length of sarcomere is important for force of contraction.
• Normal range is around 100.
• Sarcomere length: 1.2 - 2.2 mm

Actin and Myosin - Sliding Filaments

Myosin

• A diverse family of MOTOR proteins.
• Muscle myosin is myosin class II.
• There are 9 different kinds of myosin II in various muscle types.
  • 8 skeletal/cardiac.
  • 1 smooth.
• Myosin head has ATPase activity; the motor is powered by ATP hydrolysis.
• Structure includes:
  • Alpha-helical tail.
  • Heads.
  • Essential light chains.
  • Regulatory light chains.

Actin

• Exists in two forms:
  • G Actin (globular).
  • F Actin (filamentous).

Troponin and Tropomyosin

• Key regulatory proteins:
  • Tropomyosin.
  • Troponin I.
  • Troponin C.
  • Troponin T.

Steps

• Multiple steps are shown

Regulation of Contraction

• Components involved:
  • TnT.
  • Tropomyosin.
  • TnC.
  • Tnl.
  • Actin.
• Myosin binding site is key for contraction regulation.
• Ca^{2+} ions play a critical role.

Excitation-Contraction Coupling

The Neuromuscular Junction (NMJ)

• Motor neuron releases Acetylcholine (ACh).
• AChE (Acetylcholinesterase) breaks down ACh into Choline and Acetate.
• ACh binds to nAChR (nicotinic acetylcholine receptors) on the muscle.

Skeletal Muscle Fiber

• Key components (repeated for emphasis):
  • Sarcolemma.
  • Nucleus.
  • Mitochondria.
  • Myofibrils.
  • T tubule.
  • Terminal cisterna.
  • Triad.
  • Sarcoplasmic Reticulum.

Triad

• T-Tubule.
• Motor neuron releases action potential.
• nAChR is involved.
• Sarcoplasmic reticulum is adjacent.

Calcium in Muscle Cells

• Ca^{2+} enters through VSCC (Voltage-Sensitive Calcium Channels), specifically L-type calcium channels (DHP - dihydropyridine receptor).
• SERCA (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase) pumps calcium back into the sarcoplasmic reticulum using ATP.
• Calcium concentration: ~100 nM inside the cell, mM outside and in the sarcoplasmic reticulum.

Calcium Source

• Ryanodine receptor on the sarcoplasmic reticulum releases Ca^{2+}.
• DHP receptor is physically linked and interacts with the ryanodine receptor.

The DHP Receptor Tetrad

• Located in the T Tubule Membrane.
• Ryanodine Receptor is located in the SR Membrane.

Restoring Calcium Balance

• SERCA pumps Ca^{2+} back into the sarcoplasmic reticulum, maintaining low intracellular calcium levels (100 nM).

Summary: Nerve to Muscle

• Acetylcholine released by motor neuron.
• Activates nACh receptors.
• Sarcolemma depolarizes, action potential triggered, spreads to T tubules.
• DHP receptor activated, triggers ryanodine receptor.
• Calcium ions released from sarcoplasmic reticulum.
• Troponin C binds Ca^{2+} and is activated.
• Muscle contraction initiated.
• Calcium ions pumped back into SR.

Pathology of Myasthenia Gravis

• Myasthenia Gravis affects the neuromuscular junction.

Pathology

1. Receptors become internalized.
2. Destruction and simplification of the end plate.
3. Block of the acetylcholine binding sites.