Biol 2301 Lecture 11

Skeletal Muscle Function

• Produce movement and locomotion

• Provide protection and support to internal organs

• Maintain posture and stabilize joints

• Generate heat during muscle activity

• Facilitate communication through body movements

Characteristics of Muscles

• Contractility: Ability to forcibly shorten when stimulated

• Excitability: Ability to respond to stimuli (chemical)

• Extensibility: Capability to stretch beyond resting length

• Elasticity: Ability to recoil to resting length

• Plasticity: Adaptability based on usage

Skeletal Muscle Composition

• Over 600 named skeletal muscles in the body

• Each muscle is a discrete organ

Connective Tissue Components

• Epimysium: Surrounds entire muscle

• Perimysium: Surrounds bundles of muscle fibers (fascicles)

• Endomysium: Surrounds individual muscle fibers

• Tendon: Connects muscle to bone, skin, or muscle

Microanatomy of Skeletal Muscle

• Sarcolemma: Plasma membrane of muscle fiber

• Sarcoplasm: Cytoplasm containing glycosomes and myoglobin

• Myofibrils: Organizing contractile elements; composed of myofilaments

• Sarcomere: Functional unit of muscle between two Z lines

Myofilament Structure

• Thick Filaments: Composed of myosin; forms cross-bridges with actin

• Thin Filaments: Composed of actin, tropomyosin, and troponin

Motor Unit

• Composed of alpha motor neuron and muscle fibers it innervates

• Variation in number of muscle fibers depending on muscle function

Neuromuscular Junction

• Interaction point between motor neuron and muscle fiber

• Contains synaptic cleft, synaptic vesicles with acetylcholine (ACh)

Muscle Twitch

• A single contraction of a muscle fiber

• Phases: Latent period, contraction time, relaxation period

Steps in Muscle Contraction

1. Neuromuscular Junction: ACh release and binding to receptors

2. Excitation-Contraction Coupling: Action potential travels through T-tubules; Ca2+ released from sarcoplasmic reticulum

3. Crossbridge Cycling: Ca2+ triggers sliding of actin past myosin; sarcomere shortens

Contraction Mechanics

• Powerstroke: Myosin moves actin, causing contraction

• Sliding Filament Mechanism: Thin filaments slide towards center of sarcomere, shortening I band and H zone

Relaxation

• Removal of ACh by AChE; no EPP, no AP

• Ca2+ pumped back into sarcoplasmic reticulum by SERCA

Energy Systems in Muscle Metabolism

• Immediate Supplies: Phosphagen system (short burst energy, ~5-15 sec)

• Short-Term Supplies: Anaerobic cellular respiration (rapid, generates lactic acid)

• Long-Term Supplies: Aerobic cellular respiration (requires oxygen, high ATP yield)

Skeletal Muscle Function

• Produce movement and locomotion: Skeletal muscle contractions pull on bones, causing movement at joints. Examples include walking, lifting, and running.

• Provide protection and support to internal organs: Muscles form the walls of the abdominal and pelvic cavities, protecting underlying organs.

• Maintain posture and stabilize joints: Continuous low-level contractions (muscle tone) help maintain body posture and keep joints aligned.

• Generate heat during muscle activity: Muscle contractions produce heat as a byproduct, helping to maintain body temperature. Shivering is an extreme example of heat generation.

• Facilitate communication through body movements: Includes facial expressions, gestures, and writing.

Characteristics of Muscles

• Contractility: The unique ability to forcibly shorten when stimulated, involving the interaction of myofilaments.

• Excibility: The ability to respond to stimuli (e.g., neurotransmitters or hormones) by generating an electrical impulse (action potential).

• Extensibility: The capability to stretch or extend beyond their resting length, allowing for a wide range of motion, often facilitated by antagonistic muscles.

• Elasticity: The ability to recoil and return to their original resting length after stretching, due to elastic components like titin and connective tissues.

• Plasticity: The adaptability and ability to change in response to usage, such as hypertrophy (growth) with training or atrophy (shrinkage) with disuse.

Skeletal Muscle Composition

• Over $600$ named skeletal muscles in the body.

• Each muscle is a discrete organ, composed of muscle tissue, connective tissue, nerves, and blood vessels.

Levels of Organization

• Muscle: Composed of multiple fascicles.

• Fascicle: A bundle of muscle fibers.

• Muscle Fiber (Cell): An individual muscle cell.

• Myofibril: A contractile organelle within a muscle fiber.

• Myofilaments: Proteins (actin and myosin) that make up myofibrils.

Connective Tissue Components

• Epimysium: Dense irregular connective tissue that surrounds the entire gross muscle. It provides strength and protection and is continuous with tendons.

• Perimysium: Fibrous connective tissue that surrounds bundles of muscle fibers (fascicles). It contains blood vessels and nerves that supply the fascicles.

• Endomysium: Fine areolar connective tissue that surrounds individual muscle fibers. It insulates muscle fibers, containing capillaries and nerve fibers.

• Tendon: A cord-like structure of dense regular connective tissue that connects muscle to bone, skin, or other muscles. Tendons transmit the force of muscle contraction to the bone and are highly collagenous and strong.

  • Aponeuroses: Flat, sheet-like tendons that anchor muscle to muscle or muscle to bone.

Microanatomy of Skeletal Muscle

• Sarcolemma: The plasma membrane of a muscle fiber. It contains T-tubules (transverse tubules) which are invaginations that extend deep into the muscle fiber, carrying action potentials.

• Sarcoplasm: The cytoplasm of the muscle fiber, containing glycosomes (glycogen storage for energy), myoglobin (oxygen-binding protein), mitochondria for ATP production, and the sarcoplasmic reticulum.

• Myofibrils: Rod-like contractile elements composed of myofilaments. They run the entire length of the muscle fiber, making up about $80\%$ of cell volume.

• Sarcoplasmic Reticulum (SR): A specialized smooth endoplasmic reticulum that surrounds each myofibril. Its primary role is to store and release calcium ions ($Ca^{2+}$), which are essential for muscle contraction. The enlarged ends of the SR are called terminal cisternae, which abut the T-tubules.

• Sarcomere: The functional contractile unit of muscle, defined as the region between two successive Z discs (or Z lines). Its striated appearance is due to alternating A (dark) and I (light) bands. Each sarcomere contains thick and thin filaments.

  • A Band: The dark band, which contains the entire length of the thick filaments and areas where thick and thin filaments overlap.

  • I Band: The light band, which contains only thin filaments and shortens during contraction.

  • H Zone: A lighter region in the center of the A band that contains only thick filaments. It disappears during contraction.

  • M Line: A protein meshwork that runs vertically through the center of the H zone, anchoring the thick filaments.

  • Z Disc: A protein disc that connects adjacent sarcomeres and anchors the thin filaments.

Myofilament Structure

• Thick Filaments: Composed primarily of the protein myosin. Each myosin molecule has a tail and two globular heads. The myosin heads form cross-bridges with actin, contain ATPase enzymes for energy, and have binding sites for ATP and actin.

• Thin Filaments: Composed of actin, tropomyosin, and troponin.

  • Actin: Forms the backbone of the thin filament; contains globular subunits with active sites where myosin heads bind.

  • Tropomyosin: A rod-shaped protein that spirals around the actin core, blocking the myosin-binding sites on actin in a relaxed muscle, thereby preventing contraction.

  • Troponin: A globular protein complex with three subunits:

  • $Tn_I$ (inhibitory): Binds to actin.

  • $Tn_T$ (tropomyosin): Binds to tropomyosin.

  • $Tn_C$ (calcium-binding): Binds calcium ions ($Ca^{2+}$).

Motor Unit

• Composed of a single alpha motor neuron and all the muscle fibers it innervates. When the motor neuron fires an action potential, all muscle fibers in its motor unit contract simultaneously.

• The number of muscle fibers per motor neuron varies depending on muscle function. Muscles requiring fine motor control (e.g., eye muscles) have small motor units (few fibers per neuron), while those for gross motor control (e.g., thigh muscles) have large motor units (hundreds of fibers per neuron).

• Motor unit recruitment: The process of increasing the number of active motor units to increase the overall force of muscle contraction.

Neuromuscular Junction (NMJ)

• The specialized interaction point between a motor neuron and a muscle fiber, acting as a synapse where nerve impulses are transmitted to the muscle.

• Components:

  • Synaptic Cleft: The space between the axon terminal of the motor neuron and the sarcolemma of the muscle fiber.

  • Synaptic Vesicles: Located in the axon terminal, containing the neurotransmitter acetylcholine (ACh).

  • ACh Receptors: Proteins on the sarcolemma within the motor end plate that bind ACh.

  • Motor End Plate: A specialized, highly folded region of the sarcolemma at the NMJ, increasing surface area for ACh receptors.

• Process:

  1. An action potential arrives at the axon terminal of the motor neuron.

  2. Voltage-gated $Ca^{2+}$ channels open, and $Ca^{2+}$ enters the axon terminal.

  3. $Ca^{2+}$ influx causes synaptic vesicles to fuse with the presynaptic membrane, releasing ACh into the synaptic cleft.

  4. ACh diffuses across the cleft and binds to ACh receptors on the motor end plate.

  5. ACh binding opens chemically gated ion channels, allowing $Na^{+}$ influx and $K^{+}$ efflux, generating a local depolarization called an End Plate Potential (EPP).

  6. If the EPP reaches threshold, it triggers an action potential (AP) that propagates along the sarcolemma.

Muscle Twitch

• A single, brief contraction of a muscle fiber in response to a single stimulus. It may or may not lead to significant shortening depending on the load.

• Phases:

  • Latent Period: The time between stimulus application and the onset of muscle contraction. During this phase, excitation-contraction coupling occurs, but no visible tension is produced.

  • Contraction Phase: The period during which muscle fibers shorten and muscle tension increases. Cross-bridges are actively forming and cycling.

  • Relaxation Phase: The period during which muscle tension declines as $Ca^{2+}$ is pumped back into the SR, and muscle fibers return to their resting length as cross-bridge cycling stops.

Steps in Muscle Contraction

This process involves both Excitation-Contraction Coupling and the Cross-Bridge Cycle.

1. Neuromuscular Junction Events (Initiation):

   • An action potential arrives at the axon terminal of the motor neuron, leading to the release of acetylcholine (ACh).

   • ACh binds to receptors on the sarcolemma, causing a local depolarization (End Plate Potential, EPP).

   • The EPP triggers a muscle action potential (AP) that propagates along the sarcolemma.

2. Excitation-Contraction Coupling (Linking Electrical to Mechanical):

   • The action potential travels along the sarcolemma and down the T-tubules into the interior of the muscle fiber.

   • The AP reaching the T-tubules causes voltage-sensitive proteins in the T-tubule membrane to change shape.

   • These shape changes open $Ca^{2+}$ release channels in the sarcoplasmic reticulum (SR) membrane.

   • $Ca^{2+}$ is released from the SR into the sarcoplasm, surrounding the myofibrils.

3. Cross-Bridge Cycling (The Mechanical Contraction):

   • $Ca^{2+}$ binds to the $Tn_C$ subunit of troponin.

   • Troponin changes shape, pulling tropomyosin away from the myosin-binding sites on actin, thereby exposing these sites.

   • Myosin heads, already energized with ADP + Pi (from previous ATP hydrolysis), bind to the exposed active sites on actin, forming a cross-bridge.

   • Inorganic phosphate (Pi) is released, initiating the power stroke.

   • Powerstroke: The myosin head pivots and pulls the thin filament towards the M line (center of the sarcomere), causing sarcomere shortening. ADP is released.

   • A new ATP molecule binds to the myosin head, causing it to detach from actin.

   • ATP is hydrolyzed into ADP + Pi by the myosin ATPase, which re-cocks (re-energizes) the myosin head to its high-energy state.

   • This cycle repeats as long as $Ca^{2+}$ and ATP are available.

Contraction Mechanics (Sliding Filament Model)

• Sliding Filament Mechanism: Muscle contraction occurs when the thin filaments slide past the thick filaments, causing the sarcomeres to shorten.

  • During contraction, the Z discs are pulled closer together.

  • The I bands shorten, and the H zone disappears.

  • The A band's length remains constant as the thick filaments themselves do not change length.

  • This shortening process occurs simultaneously in all sarcomeres along a myofibril, leading to the shortening of the entire muscle fiber and ultimately the whole muscle.

Relaxation

• The neurotransmitter ACh is rapidly removed from the synaptic cleft by the enzyme acetylcholinesterase (AChE), preventing continuous muscle contraction. This stops the generation of further EPPs and APs.

• $Ca^{2+}$ is actively pumped back into the sarcoplasmic reticulum (SR) by SERCA (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase) pumps, which requires ATP.

• As sarcoplasmic $Ca^{2+}$ levels drop, $Ca^{2+}$ detaches from troponin.

• Tropomyosin moves back to block the myosin-binding sites on actin.

• Myosin can no longer bind to actin, and the cross-bridge cycle ceases. The muscle fiber then relaxes and passively lengthens due to its elasticity and antagonistic muscle action.

Energy Systems in Muscle Metabolism

Muscles require a continuous supply of ATP for all aspects of contraction (myosin cross-bridge cycling) and relaxation ($Ca^{2+}$ pumps, maintaining ion gradients). There are three main energy systems:

• Immediate Supplies: Phosphagen System (Creatine Phosphate System)

  • Description: Used for very short, intense bursts of activity (e.g., $5-15$ seconds, like a 100m sprint or heavy weightlifting).

  • Mechanism: Creatine kinase rapidly transfers a phosphate group from creatine phosphate (CP) to ADP to generate ATP.

  • $CP + ADP \rightleftharpoons ATP + Creatine$

  • Characteristics: Very fast, but provides a very limited and rapidly depleted ATP supply.

• Short-Term Supplies: Anaerobic Cellular Respiration (Glycolysis)

  • Description: Used when immediate ATP is depleted and oxygen supply is limited (e.g., high-intensity activity lasting $30-60$ seconds).

  • Mechanism: Glucose (from blood or muscle glycogen stores) is broken down into two pyruvate molecules.

  • ATP Yield: Generates a net of $2$ ATP molecules per glucose.

  • Byproduct: If oxygen is not sufficiently available, pyruvate is converted into lactic acid, which can accumulate and contribute to muscle fatigue and soreness.

  • Characteristics: Faster than aerobic respiration but much less efficient in terms of ATP yield per glucose.

• Long-Term Supplies: Aerobic Cellular Respiration (Oxidative Phosphorylation)

  • Description: The predominant energy system for prolonged, moderate-intensity activity (e.g., endurance sports).

  • Mechanism: Requires oxygen. Occurs in the mitochondria, where glucose, fatty acids, and sometimes amino acids are completely broken down to $CO<em>2$ and $H</em>2O$.

  • ATP Yield: Generates a large amount of ATP (up to $32$ ATP per glucose molecule).

  • Characteristics: Slower than anaerobic respiration but provides a sustained and efficient supply of ATP for longer durations, as long as oxygen and fuel are available.