Muscle Contraction and Neuromuscular Physiology

Course Administration and Grade Calculation

• Canvas Grade Discrepancies: Students are warned that grades displayed on Canvas are often incorrect because the system does not properly categorize extra credit. It treats extra credit as a required component, meaning if a student misses an extra credit question, Canvas counts it against them.
• Grade Calculation Methodology:
  • Currently, grades are based on an average, though the final course grade will be determined by a total point system.
  • Extra credit points are already included in the total points column on Canvas.
  • Canvas has already dropped the lowest lecture test grade from the calculation.
• Current Possible Points (Mid-Term Breakdown):
  • Lecture Tests: The two highest tests out of three taken are counted, totaling a maximum of $200$ points.
  • Lab Tests: Two lab tests at $75$ points each have been completed, totaling $150$ points.
  • Total Possible Points to date: $350$ points.
  • Calculation Formula: $\text{Current Grade} = \frac{\text{Total Points}}{\text{350}} \times 100$
• Drop Deadline: The last day to drop the course with a "W" (withdrawal) is exactly one week from the current Monday, which is only one week before finals.
• Post-Drop Recommendations: If a student chooses to drop to protect their GPA, the instructor encourages them to continue attending lectures and labs for the remainder of the semester. Since tuition is already paid, staying allows the student to be familiar with the material when they retake the class, removing the pressure of memorizing information within $24$ hours.

Introduction to Cellular Electrical Potentials

• Electrical Gradients: All living cells possess electrical gradients across their membranes, meaning the charge inside the cell is different from the outside.
• Membrane Potential:
  • For most cells, the potential ranges between $-60$ and $-90\,mV$ (millivolts).
  • A millivolt is defined as $\frac{1}{1000}$ of a volt.
  • For the purpose of this course, muscle cells and neurons are considered to have a resting membrane potential of $-70\,mV$.
• The Sodium-Potassium Pump: The inside of the cell is more negative because the pump moves three sodium ($Na^+$) ions out for every two potassium ($K^+$) ions it brings in. This net loss of positive charge makes the interior negative. This potential is maintained despite "leaky" channels by other balancing ion movements.
• Action Potential: In neurons and muscle cells, opening ion channels creates a special electrical current known as an action potential. This is a "zap" of electricity that controls muscle contraction.

Gated Ion Channels

• Leaky Channels (Open Channels): These are always open and allow ions to move freely.
• Gated Channels: These possess a mechanism to open or close in response to specific triggers.
  • Ligand-Gated Channels: Open or close in response to a chemical signal (ligand), such as acetylcholine ($ACh$).
  • Mechanically Gated Channels: Open in response to physical movement, such as pinching or pulling (to be discussed in Anatomy II).
  • Voltage-Gated Channels: Open or close in response to changes in the electrical charge (current).

Anatomy of the Neuromuscular Junction (NMJ)

• The Synapse: A synapse is any meeting point between a neuron's axon and another cell.
  • Neuromuscular Junction: A synapse between a neuron and a skeletal muscle cell.
  • Neuroglandular Junction: A synapse between a neuron and a gland cell.
• Axon Terminal Components: The end of the neuron's axon is a knob-like structure with multiple names: axon terminal, synaptic terminal, synaptic knob, or terminal bouton (French for button).
• Synaptic Cleft: The microscopic space between the axon terminal and the muscle cell surface. Though small, electrical current cannot "jump" this gap; it must be converted into a chemical signal.
• Motor End Plate: The specific part of the muscle cell membrane (sarcolemma) that is wavy and located directly underneath the synaptic terminal.
• Triad System:
  • T-Tubules (Transverse Tubules): Invaginations of the sarcolemma that carry the action potential deep into the cell.
  • Sarcoplasmic Reticulum (SR): A modified smooth endoplasmic reticulum that stores calcium ($Ca^{2+}$).
  • Terminal Cisternae: Thickened ends of the SR that flank a T-tubule.
  • Triad Definition: One T-tubule plus two flanking terminal cisternae.

The Mechanism of Muscle Contraction (The "Bedtime Story")

Step 1: Neural Control and Signal Transmission

• An action potential travels from the brain down the axon to the axon terminal.
• This electrical current opens voltage-gated calcium channels on the neuron.
• Calcium enters the neuron, which triggers synaptic vesicles to move to the surface and release acetylcholine (ACh) into the synaptic cleft via exocytosis.

Step 2: Excitation of the Muscle Cell

• ACh (the ligand) drifts across the cleft and binds to ligand-gated sodium channels on the motor end plate of the muscle cell.
• These channels open, allowing a rush of sodium ($Na^+$) into the muscle cell because the interior is negative and sodium concentrations are high outside.
• The influx of sodium creates a new action potential that spreads across the sarcolemma.

Step 3: Signal Termination

• The enzyme acetylcholinesterase (AChE) immediately breaks down ACh into acetic acid (vinegar) and choline.
• This terminates the signal, closing the sodium channels and allowing the neuron to recycle the components for future use.

Step 4: Excitation-Contraction Coupling

• The new action potential travels down the sarcolemma and into the T-tubules.
• The current triggers the opening of voltage-gated calcium channels on the terminal cisternae of the sarcoplasmic reticulum.
• Calcium flooded in the SR ($2,000$ to $3,000$ times higher concentration than the cytosol) rushes out into the sarcoplasm via diffusion.

Step 5: The Sarcomere Response

• Calcium binds to troponin (the "bouncer").
• Troponin changes shape, which pulls on the tropomyosin (the "rope").
• This movement uncovers the active binding sites on the actin (thin filament).

Step 6: The Contraction Cycle (Cross-Bridge Cycling)

• Myosin Heads: Already energized by breaking down an ATP into ADP and phosphate ($P_i$), the myosin heads reach up and grab the binding sites on actin, forming a cross-bridge.
• Power Stroke: The myosin head flexes at its hinge, pulling the actin filament toward the M-line (center of the sarcomere). This releases the stored ADP and phosphate.
• Detachment: A new ATP molecule must bind to the myosin head to make it release the actin.
• Reactivation: The myosin head breaks the new ATP down again to reset itself for another pull.

Sliding Filament Theory

• During contraction, filaments do not shrink; they slide past one another. The structural changes in the sarcomere are as follows:
  • I-Band: Gets smaller (contains only thin filaments).
  • H-Band: Gets smaller (contains only thick filaments).
  • Zone of Overlap: Gets larger.
  • Z-Lines: Move closer to the M-line.
  • A-Band: Remains constant (the length of the thick filament does not change).
• Origin and Insertion: To produce movement, one end of the muscle is anchored to a stationary bone (origin), and the other is attached to a bone that moves (insertion).

Energy Sources for Contraction

• Muscles cannot store ATP; they must generate it continuously. Three methods exist:
  1. Direct Phosphorylation: Creatine acts as a storage molecules for phosphate. It takes a phosphate from ATP during rest to become creatine phosphate. During activity, the enzyme creatine kinase transfers the phosphate back to ADP to create ATP. This provides about $15$ seconds of energy.
  2. Anaerobic Metabolism (Glycolysis): Occurs in the cytoplasm without oxygen. It breaks one glucose into two pyruvate molecules, yielding a net of $2$ ATP. If oxygen is absent, pyruvate is converted to lactate (lactic acid), causing muscle soreness.
  3. Aerobic Metabolism: Occurs in the mitochondria and requires oxygen. It involves the Citric Acid Cycle (Krebs Cycle) and the Electron Transport Chain. It is highly efficient, producing approximately $34$ to $36$ ATP per glucose molecule. At rest, muscles prefer to burn fatty acids (triglycerides), which provide about $120\,ATP$ each.

Muscle Fatigue and Recovery

• Physiological Fatigue: Occurs when ATP is completely depleted, metabolic reserves are exhausted, and pH drops due to lactic acid buildup. This rarely happens except in extreme athletes (marathoners).
• Psychological Fatigue: Most common; the mind perceives pain or burning and stops the activity before physical limits are reached.
• Recovery Period: The time needed for muscles to return to pre-exertion states.
  • Lactic Acid Removal: Lactate is transported to the liver, where it is converted back into pyruvate and then glucose (the Cori Cycle).
  • Oxygen Debt: Technically known as Excess Post-exercise Oxygen Consumption (EPOC); the body requires extra oxygen after exercise to restore ATP levels and clear lactate.
• Rigor Mortis: A post-mortem state starting a few hours after death. Because ATP production stops, the calcium pumps fail and calcium leaks out of the SR. Myosin heads bind to actin, but because there is no new ATP to cause detachment, the muscles lock in a contracted state. This peaks at $12$ hours and ends after $12$ to $36$ hours when enzymes decompose the protein heads.

Muscle Adaptation and Contraction Types

• Hypertrophy: An increase in muscle size caused by resistance training which adds more myofibrils to existing muscle cells. It does not increase the number of cells.
• Atrophy: A decrease in muscle size and strength due to lack of use; the body absorbs muscle protein to reduce metabolic load.
• Isotonic Contractions: Tension remains constant while the muscle length changes.
  • Concentric: Muscle shortens (e.g., the "up" phase of a bicep curl).
  • Eccentric: Muscle lengthens while under tension (e.g., lowering a heavy weight slowly).
• Isometric Contractions: The muscle length remains the same while tension increases (e.g., pushing against a wall or "bulking up" a muscle for display).

Questions & Discussion

• Student Question: "I just hope for some other grade. So I ended up… do I add, like, my extra credit points to…?"
• Instructor Response: "You don't add anything. This course should already be added up for you. Every point in your total on Canvas already has every point you're getting. Don't manually add stuff because you might add it wrong. The total on Canvas is right, even if the percentage average is wrong."
• Student Question: "Where's the body farm at? Where is it?"
• Instructor Response: "It's up near College Station [Texas]. But you have to have special permission to go there. … People donate their bodies or unidentified bodies are sent there. They leave them outside in Texas weather… to document every step of decomposition. So when they find a victim, they can match it up to find the time of death."