Table of Contents
Muscle cells (muscle fibers) are highly specialized excitable and contractile cells. In this chapter, the focus is on how they convert electrical signals and chemical energy into mechanical force and movement.
Types of Muscle Cells and Their Functional Specializations
In vertebrates and humans, three basic muscle cell types are distinguished, each with characteristic functional properties:
Skeletal Muscle Cells (Striated Skeletal Muscle)
- Control: Mostly under voluntary (somatic) control.
- Structure:
- Long, cylindrical fibers, often many centimeters in length.
- Multinucleated: many nuclei at the cell periphery.
- Regular banding pattern (striations) due to orderly arrangement of contractile proteins.
- Function:
- Responsible for body movements, posture, facial expressions.
- Can contract rapidly and with great force.
- Fatigue depends on fiber type (e.g., fast vs. slow fibers; details in muscle movement).
Cardiac Muscle Cells (Heart Muscle)
- Control: Involuntary, rhythmically active, modulated by the autonomic nervous system and hormones.
- Structure:
- Short, branched cells.
- Usually one centrally located nucleus per cell.
- Striated like skeletal muscle, but cells are interconnected by intercalated discs (special cell-cell junctions).
- Function:
- Form a functional syncytium: excitation spreads rapidly from cell to cell.
- Generate rhythmic, coordinated contractions pumping blood.
- High resistance to fatigue.
Smooth Muscle Cells
- Control: Involuntary; controlled by autonomic nervous system, local factors, and hormones.
- Structure:
- Spindle-shaped (fusiform) cells.
- One central nucleus.
- No visible striations under light microscopy (different arrangement of contractile proteins).
- Function:
- Found in walls of hollow organs (intestines, blood vessels, uterus, airways).
- Contractions are slower, often sustained (tonic), and can occur in waves.
- Important for peristalsis, regulation of vessel diameter, and other autonomic functions.
Despite structural differences, all muscle cells use similar molecular mechanisms: excitation triggers a rise in intracellular calcium concentration, which activates interaction between actin and myosin filaments and generates force.
The Contractile Apparatus: Myofibrils and Sarcomeres
The ability of muscle cells to contract is based on highly ordered assemblies of proteins:
Myofibrils
- Long, thread-like structures running parallel through the muscle fiber.
- Composed of repeating units called sarcomeres.
- In skeletal and cardiac muscle, the regular arrangement of myofibrils produces the characteristic striations.
Sarcomere
- The basic contractile unit of striated muscle.
- Bordered by Z-discs (Z-lines).
- Contains:
- Thin filaments: mainly actin, plus regulatory proteins tropomyosin and troponin (in skeletal and cardiac muscle).
- Thick filaments: myosin molecules forming a central bundle.
- Overlapping arrangement of thin and thick filaments is responsible for contraction via the sliding filament mechanism.
Smooth muscle also contains actin and myosin, but they are arranged in networks anchored to the plasma membrane and intracellular dense bodies instead of well-defined sarcomeres. This allows contraction in multiple directions, suitable for hollow organs.
Molecular Basis of Contraction: Sliding Filament Theory
The core of muscle function is the cyclic interaction between myosin heads on the thick filaments and actin on the thin filaments:
- Resting State
- In skeletal and cardiac muscle, tropomyosin blocks the myosin-binding sites on actin.
- Myosin heads are in a “cocked” high-energy state, bound to ADP and inorganic phosphate ($\text{Pi}$), but cannot bind strongly to actin.
- Cross-Bridge Formation
- When binding sites on actin become available, myosin heads attach to actin, forming cross-bridges.
- Power Stroke
- The myosin head pivots, pulling the actin filament toward the center of the sarcomere.
- ADP and $\text{Pi}$ are released.
- This movement shortens the sarcomere and generates force.
- Detachment
- A new ATP molecule binds to the myosin head, causing it to detach from actin.
- Re-cocking of the Myosin Head
- ATP is hydrolyzed to ADP and $\text{Pi}$.
- The energy released re-cocks the myosin head into the high-energy conformation, ready for another cycle.
As long as:
- Calcium concentration remains elevated in the cytosol, and
- ATP is available,
the cycle repeats and the filaments slide past each other. The sarcomeres, myofibrils, and ultimately the entire muscle cell shorten, producing contraction.
In smooth muscle, the same fundamental interaction of actin and myosin occurs, but it is regulated differently (see below).
Role of Calcium Ions in Contraction and Relaxation
Calcium ions ($\text{Ca}^{2+}$) are the key link between electrical excitation of the muscle cell membrane and mechanical contraction.
Intracellular Calcium Stores and Membranes
- Sarcoplasmic reticulum (SR): Specialized endoplasmic reticulum in muscle cells; stores $\text{Ca}^{2+}$.
- Transverse tubules (T-tubules): Invaginations of the cell membrane (sarcolemma) in skeletal and cardiac muscle.
- Conduct action potentials deep into the interior of the fiber.
- Bring membrane electrical changes close to the SR.
Excitation–Contraction Coupling in Striated Muscle
The sequence from action potential to contraction:
- Action Potential at the Sarcolemma
- An action potential (AP), generated at the neuromuscular junction or pacemaker system, spreads over the muscle cell membrane.
- Propagation into T-Tubules
- The AP travels along T-tubules.
- Voltage-sensitive proteins in the T-tubule membrane sense the depolarization.
- Calcium Release from the Sarcoplasmic Reticulum
- In skeletal muscle: Voltage sensors mechanically or via coupling open $\text{Ca}^{2+}$-release channels (ryanodine receptors) in the SR membrane.
- In cardiac muscle: $\text{Ca}^{2+}$ entry from the extracellular fluid triggers additional $\text{Ca}^{2+}$ release from the SR (calcium-induced calcium release).
- Rise in Cytosolic Calcium
- $\text{Ca}^{2+}$ concentration in the cytoplasm increases sharply.
- Activation of the Contractile Apparatus
- In skeletal and cardiac muscle:
- $\text{Ca}^{2+}$ binds to troponin C.
- Tropomyosin shifts, exposing myosin-binding sites on actin.
- Cross-bridge cycling begins → contraction.
- Relaxation
- After the AP ends, $\text{Ca}^{2+}$-ATPases in the SR membrane pump $\text{Ca}^{2+}$ back into the SR.
- Cytosolic $\text{Ca}^{2+}$ concentration falls.
- Tropomyosin again covers the binding sites on actin.
- No new cross-bridges form; existing ones detach → the muscle relaxes and returns to its resting length (often aided by elastic elements and opposing muscles).
Calcium Regulation in Smooth Muscle
Smooth muscle does not use the troponin–tropomyosin system for $\text{Ca}^{2+}$ regulation in the same way:
- $\text{Ca}^{2+}$ enters from the extracellular fluid and is also released from internal stores.
- $\text{Ca}^{2+}$ binds to calmodulin (instead of troponin).
- The $\text{Ca}^{2+}$–calmodulin complex activates myosin light-chain kinase (MLCK).
- MLCK phosphorylates the regulatory light chain of myosin.
- Phosphorylated myosin can now form cross-bridges with actin → contraction.
- Relaxation occurs when myosin light-chain phosphatase removes the phosphate group and $\text{Ca}^{2+}$ levels decrease.
This regulation allows smooth muscle:
- To respond to a variety of signals (nerve impulses, hormones, stretch, local metabolites).
- To maintain tension over long periods with relatively low energy consumption.
Energy Supply for Muscle Cells
Muscle contraction requires continuous ATP:
- For the cross-bridge cycle (detachment and re-cocking of myosin heads).
- For ion pumps (especially $\text{Ca}^{2+}$-ATPases in the SR and $\text{Na}^+/\text{K}^+$ pumps in the sarcolemma).
Muscle cells use multiple sources for ATP regeneration (detailed mechanisms are covered elsewhere):
- Immediate Energy: Phosphagen System
- Creatine phosphate (phosphocreatine) donates phosphate to ADP:
$$\text{ADP} + \text{Creatine phosphate} \rightarrow \text{ATP} + \text{Creatine}$$ - Provides ATP very quickly, but only for a few seconds of maximal effort.
- Anaerobic Glycolysis
- Glucose → pyruvate (and under anaerobic conditions → lactate).
- Provides ATP rapidly; supports short, intense activities; limited by metabolite accumulation.
- Aerobic Metabolism (Cellular Respiration)
- Complete oxidation of carbohydrates, fats (and in some cases amino acids).
- Slower ATP production but highly efficient.
- Dominant in prolonged, moderate-intensity activity and in heart muscle.
Cardiac muscle relies almost exclusively on aerobic metabolism and is rich in mitochondria and myoglobin. Skeletal muscle fibers differ in mitochondrial content and metabolic profile (e.g., “slow oxidative” vs. “fast glycolytic” fibers), which is functionally important for different types of movement.
Functional Properties of Muscle Cells
Excitability and Conductivity
- Muscle cells are excitable: they respond to stimuli (e.g., from motor neurons, pacemaker cells, stretch, or hormones) with changes in membrane potential.
- Skeletal and cardiac muscle cells can conduct excitation along their membranes and, via T-tubules or cell-cell connections, coordinate contraction of the whole fiber or tissue.
Contractility and Force Generation
- Force is produced whenever cross-bridges cycle and filaments slide relative to one another.
- The amount of force a muscle cell can produce depends on:
- The number of cross-bridges formed at a given time.
- The initial length of sarcomeres (optimal overlap of actin and myosin).
- The frequency of stimulation (summation and tetanus in skeletal muscle).
- The metabolic state (ATP availability, $\text{Ca}^{2+}$ handling).
Elasticity and Extensibility
- Even while generating force, muscle cells contain elastic elements (e.g., titin in sarcomeres, connective tissue around fibers).
- These contribute to:
- Returning to resting length after stretching or contraction.
- Storing and releasing elastic energy (important in movements like jumping or running).
Plasticity and Adaptation
- Muscle cells can adapt functionally to use:
- Increased load → hypertrophy, improved contractile capacity.
- Endurance training → more mitochondria, improved blood supply, increased fatigue resistance.
- Smooth muscle can also adapt structurally and functionally to long-term changes in stretch or pressure (e.g., in blood vessels or uterus).
Coordination with the Nervous and Endocrine Systems
While details of neural control and hormone action are treated in other chapters, functionally important aspects for muscle cells include:
- Skeletal muscle:
- Activated by motor neurons at neuromuscular junctions.
- Each action potential in a motor neuron can trigger a contraction in its innervated muscle fibers.
- Fine movement control depends on motor unit size and recruitment.
- Cardiac muscle:
- Generates its own rhythmic excitation (pacemaker cells).
- Autonomic nervous system and hormones modulate heart rate and contractility.
- Smooth muscle:
- Often activated not only by nerves but also by hormones, paracrine factors, and direct response to stretch.
- Can exhibit spontaneous rhythmic activity (pacemaker regions) and coordinated waves of contraction.
In all cases, the function of muscle cells is to integrate incoming signals, adjust intracellular calcium and energy use, and thereby produce precisely controlled mechanical work at the level of cells, organs, and the whole organism.