Table of Contents
Overview: From Excitation to Movement
Muscle movement is the conversion of chemical energy into mechanical work. In this chapter, we follow what happens in muscle tissue once an excitation signal (an action potential) has arrived at a muscle cell and been transmitted to it. The focus here is on how force and movement are actually generated at the cellular and molecular level.
We mainly use skeletal muscle as the model, then highlight key differences to smooth and cardiac muscle.
Structural Basis of Movement in Skeletal Muscle
From Muscle to Myofibril
Skeletal muscle is organized hierarchically:
- Whole muscle → bundles of muscle fibers
- Each muscle fiber → a single, very long, multinucleated cell
- Inside each muscle fiber → many myofibrils
Each myofibril is composed of repeating units called sarcomeres. Sarcomeres are the smallest contractile units of skeletal (and cardiac) muscle.
The Sarcomere: Contractile Unit
A sarcomere is delimited by two dark Z-discs (Z-lines). Within a sarcomere:
- Thin filaments
- Mainly actin, plus regulatory proteins tropomyosin and troponin
- Anchored at the Z-disc
- Thick filaments
- Mainly myosin (myosin II in skeletal muscle)
- Located in the center of the sarcomere
Regions visible in microscope images (light/dark bands):
- I-band: Only thin filaments (actin), spans across two sarcomeres, includes Z-disc
- A-band: Length of thick filaments (myosin), includes areas of overlap with actin
- H-zone: Central part of A-band where only thick filaments are present (no actin overlap)
- M-line: Middle of the sarcomere; thick filaments are cross-linked here
During contraction, the sarcomere shortens as thin and thick filaments slide past each other; the filaments themselves do not shrink.
Excitation–Contraction Coupling in Skeletal Muscle
This is the chain of events linking an action potential in a motor neuron to contraction of the muscle fiber.
1. Neuromuscular Transmission (Start Point for This Chapter)
At the neuromuscular junction:
- A motor neuron action potential reaches the terminal
- The neurotransmitter acetylcholine (ACh) is released
- ACh binds to receptors on the muscle fiber membrane (sarcolemma)
- This triggers an action potential in the muscle fiber
Excitation and synaptic transmission themselves are handled in other chapters; we treat this as the starting signal.
2. Propagation of the Muscle Action Potential
- The muscle action potential spreads along the sarcolemma
- It invaginates into the cell interior via T-tubules (transverse tubules), which are extensions of the plasma membrane
T-tubules are closely associated with the sarcoplasmic reticulum (SR), a specialized endoplasmic reticulum in muscle cells that stores Ca²⁺.
3. Calcium Release from the Sarcoplasmic Reticulum
At specialized junctions (triads):
- An action potential in the T-tubule activates voltage-sensitive proteins in its membrane
- These interact with Ca²⁺-release channels in the adjacent SR membrane (ryanodine receptors)
- Result: Rapid release of Ca²⁺ from SR into the sarcoplasm (the cytoplasm of the muscle fiber)
The rise in cytosolic Ca²⁺ concentration is the direct trigger for contraction.
Sliding Filament Theory: How Filaments Move
Role of Troponin and Tropomyosin
At rest, contraction is inhibited:
- Tropomyosin lies along the actin filament, covering the myosin-binding sites on actin
- Troponin complex (with subunits that bind actin, tropomyosin, and Ca²⁺) is attached to tropomyosin
When Ca²⁺ concentration rises:
- Ca²⁺ binds to troponin
- Troponin changes shape
- Tropomyosin is moved away from the myosin-binding sites on actin
- Myosin heads can now bind to actin → cross-bridge formation
Thus, in skeletal muscle, Ca²⁺ regulates access of myosin to its binding sites on actin.
Cross-Bridge Cycle (Actin–Myosin Interaction)
Movement is produced by repeated cyclic interactions between myosin heads on thick filaments and actin on thin filaments. Each cycle uses one ATP molecule per myosin head.
Steps of the Cross-Bridge Cycle
- Resting state – myosin with ADP + Pi
- Myosin head contains bound ADP and inorganic phosphate (Pi)
- Myosin is in a “cocked” (high-energy) conformation
- Binding site on actin is blocked by tropomyosin (low Ca²⁺)
- Cross-bridge formation
- Ca²⁺ binding to troponin uncovers actin’s binding site
- Myosin head binds to actin, forming a cross-bridge
- Power stroke
- Myosin head releases Pi and then ADP
- The head pivots, pulling the actin filament toward the center of the sarcomere
- This is the power stroke that generates force and shortens the sarcomere
- Detachment
- A new ATP molecule binds to myosin
- ATP binding reduces myosin’s affinity for actin
- Myosin detaches from actin
- Re-cocking of the myosin head
- ATP is hydrolyzed:
$$ \text{ATP} \rightarrow \text{ADP} + \text{Pi} $$ - Energy released is used to “re-cock” the myosin head into the high-energy conformation
- The cycle can repeat if Ca²⁺ is still elevated and actin-binding sites remain exposed
Rigor Mortis and ATP Dependence
- If ATP is not available, myosin heads remain bound to actin after the power stroke
- This leads to a rigid state (rigor), observed in rigor mortis after death, when ATP production stops
- This illustrates that ATP is required for detachment, not just for force production.
Regulation of Contraction Strength in Skeletal Muscle
Individual muscle fibers can only produce all-or-none action potentials, but the force of contraction can be graded at the level of the whole muscle.
Motor Units and Recruitment
- A motor unit: one motor neuron and all muscle fibers it innervates
- Small motor units → fine control (e.g., eye muscles)
- Large motor units → powerful, coarse movements (e.g., thigh muscles)
Muscle force increases by:
- Recruiting more motor units (more fibers activated)
- Preferentially recruiting larger motor units at higher demand
Temporal Summation and Tetanus
Due to the way Ca²⁺ and cross-bridge cycling behave, the timing of action potentials affects force:
- A single action potential → twitch: a brief, weak contraction
- If new action potentials arrive before the twitch has fully relaxed:
- Ca²⁺ remains elevated
- Force from successive twitches summates (temporal summation)
- At high stimulation frequencies:
- Individual twitches fuse into a sustained contraction called tetanus
- In complete tetanus, force is maximal and steady
Physiological movements often rely on asynchronous stimulation of different motor units, producing smooth, sustained contractions.
Muscle Length, Load, and Types of Contraction
Length–Tension Relationship
Force depends on initial sarcomere length:
- At optimal length, there is maximal overlap between actin and myosin:
- Many cross-bridges can form → maximal active tension
- If the muscle is too short:
- Filaments overlap too much; cross-bridge formation is hindered
- If too stretched:
- Overlap between thick and thin filaments is reduced; fewer cross-bridges can form
This explains why muscles have an optimal operating length for generating force.
Types of Contraction
Depending on how muscle length changes under load:
- Isometric contraction
- Muscle develops tension but does not change length
- Example: holding a heavy object without moving it
- Isotonic contraction
- Muscle changes length while the load remains approximately constant
- Example: lifting a dumbbell at steady speed
- Subtypes in common usage:
- Concentric: muscle shortens while producing force (lifting)
- Eccentric: muscle lengthens while active (controlled lowering)
Eccentric actions often produce higher forces and contribute significantly to muscle soreness and adaptation.
Ending Contraction: Relaxation
Relaxation requires active processes:
- Stopping the excitation
- Motor neuron stops firing
- Acetylcholine in the synaptic cleft is broken down by acetylcholinesterase
- Reuptake of Ca²⁺
- Ca²⁺-ATPase pumps (SERCA) in SR membrane actively transport Ca²⁺ from the cytosol back into SR:
$$ \text{Ca}^{2+}_{\text{cytosol}} + \text{ATP} \rightarrow \text{Ca}^{2+}_{\text{SR}} + \text{ADP} + \text{Pi} $$ - Cytosolic Ca²⁺ concentration falls
- Blocking of myosin-binding sites
- With less Ca²⁺ bound, troponin returns to its resting conformation
- Tropomyosin again covers myosin-binding sites on actin
- Cross-bridge cycling stops; the muscle relaxes and returns to its resting length (with help from elastic components and antagonistic muscles)
Energy Supply for Muscle Movement
Muscle cells use ATP very quickly during intense activity. ATP must be continuously regenerated from other energy sources.
Immediate Source: ATP and Creatine Phosphate
- ATP stores are small and only last for a few seconds of maximal effort
- Creatine phosphate (phosphocreatine) buffers ATP:
$$ \text{Creatine}\,\text{phosphate} + \text{ADP} \rightleftharpoons \text{Creatine} + \text{ATP} $$ - This reaction is catalyzed by creatine kinase
- Provides rapid ATP regeneration for short, intense bursts (e.g., sprint start)
Short- to Medium-Term: Anaerobic Glycolysis
- Glycolysis breaks down glucose to pyruvate, producing ATP without needing oxygen
- Under conditions of limited oxygen or high intensity:
- Pyruvate is converted to lactate
- Yields ATP rapidly, but less efficiently than full oxidation
- Contributes to acid–base changes and fatigue
(Details of glycolysis and fermentation are covered in metabolism chapters.)
Long-Term: Aerobic Oxidation
- With sufficient oxygen, pyruvate (and fatty acids) is further broken down in:
- Citric acid cycle
- Electron transport chain
- Produces much more ATP per molecule of fuel
- Supports endurance activities and sustained contractions
The mix of these sources used at any time depends on intensity and duration of activity.
Differences in Muscle Movement: Skeletal vs. Cardiac vs. Smooth Muscle
Although all muscle types use actin–myosin interactions, they differ in control mechanisms, speed, and pattern of contraction.
Cardiac Muscle
- Found only in the heart
- Sarcomeric organization similar to skeletal muscle (striated)
- Key features for movement:
- Involuntary and rhythmically active
- Cells are electrically coupled via gap junctions at intercalated discs
- Action potentials can spread from cell to cell, allowing the heart to contract as a functional syncytium
- Ca²⁺ for contraction comes both from SR and from extracellular space (via membrane channels)
- Long refractory period prevents tetanus → essential for rhythmic pumping
Cardiac contraction is finely adjusted by autonomic nerves and hormones, but is not under conscious control.
Smooth Muscle
- Found in walls of blood vessels, intestines, airways, uterus, etc.
- Not organized in obvious sarcomeres; non-striated appearance
- Still uses actin and myosin, but with different arrangement and regulation:
- No troponin; regulation via phosphorylation of myosin and calmodulin (a Ca²⁺-binding protein)
- Contraction can be slow but sustained with low energy consumption
- Can maintain tonic contractions (e.g., in blood vessels) for long periods
- Often responds to autonomic nerves, hormones, and local factors rather than to voluntary commands
Coordination of Movement at the Organism Level (Brief View)
The muscle’s internal mechanisms must be coordinated with signals from the nervous system and the mechanical requirements of the body:
- Antagonistic muscle pairs (e.g., biceps and triceps) produce opposite movements at joints
- Central nervous system programs movement sequences, adjusts:
- Which muscles are active
- The timing and pattern of action potentials
- Feedback from proprioceptors (sensors in muscles and tendons) helps fine-tune force and position
Details of how nervous systems plan and coordinate such activity are treated in other chapters; here we emphasize that muscle movement results from the integration of excitation, cross-bridge cycling, Ca²⁺ dynamics, and energy supply within the muscle cell.