The Physiology of Excitable Cells: Action Potentials and Muscle Structure

Action Potential: Cellular Electrical Signals

An action potential is a rapid, transient electrical potential change that occurs exclusively in excitable cells, such as neurons and muscle cells. It is fundamental for transmitting information throughout the nervous system and initiating muscle contraction.

Neuron Operation and Signal Transmission

In neurons, excitation typically originates in the dendrites or soma (cell body), and this electrical information is then transmitted along the axon. Many axons are covered with Schwann cells, forming a myelin sheath that allows for faster signal propagation (myelination). It's important to distinguish that when referring to nerve fibers, we mean axons, whereas muscle fibers refer to muscle cells.

Schwann cells discontinuously myelinate axons, creating gaps known as Nodes of Ranvier. Neurons possess various transmembrane transport proteins, including ion channels, which are crucial for generating and propagating action potentials.

Ion Channels and Membrane Permeability

Ion channels are specialized proteins that regulate the flow of ions across the cell membrane. Their opening and closing can depend on different stimuli:

• Voltage-gated channels: Open or close in response to changes in the electrical potential difference across the membrane.
• Chemically-gated channels (ligand-gated channels): Open or close when specific chemical molecules (ligands) bind to them.
• Passive diffusion channels (leak channels): Are always open, allowing a continuous, albeit small, flow of ions.

Mechanism of Action Potential Generation

Voltage-gated sodium (Na+) and potassium (K+) channels are primarily responsible for the initiation and propagation of the action potential. When significant changes in cell membrane permeability occur, the membrane potential is restored through intrinsic cellular mechanisms.

Voltage-gated Na+ channels can exist in three states: open, closed, or inactive. Voltage-gated K+ channels typically have two states: open or closed.

The process unfolds as follows:

1. Depolarization to Threshold: If a stimulus causes the membrane potential to depolarize sufficiently to reach the threshold potential, it triggers the action potential.
2. Rapid Depolarization (Rising Phase): Upon reaching the threshold, voltage-gated Na+ channels rapidly open (they activate faster than K+ channels). This influx of Na+ ions causes a rapid and significant depolarization, making the inside of the cell positive.
3. Repolarization (Falling Phase): Almost immediately after opening, Na+ channels begin to rapidly inactivate. Concurrently, voltage-gated K+ channels open, allowing K+ ions to leave the cell. This efflux of positive charge repolarizes the membrane, bringing the potential back towards its resting state.
4. Hyperpolarization (Undershoot): As the membrane repolarizes, K+ channels remain open for a brief period even after the resting potential is reached. This continued K+ efflux leads to a temporary hyperpolarization, where the membrane potential becomes more negative than the resting potential.
5. Restoration of Resting Potential: The mechanisms regulating membrane potential, including the Na+/K+ pump, work to restore the initial electronegativity as the K+ channels eventually close.

Refractory Periods

During and immediately after an action potential, the excitable cell enters a refractory period, during which its ability to generate another action potential is altered:

• Absolute Refractory Period: During this phase, no stimulus, regardless of its strength, can trigger a new depolarization. This is due to the inactivation of Na+ channels.
• Relative Refractory Period: Occurs during the hyperpolarization phase. A stronger-than-normal stimulus is required to trigger a new action potential because the membrane is hyperpolarized and some K+ channels are still open.

Sarcolemma: Muscle Cell Membrane

The sarcolemma is the specialized plasma membrane of a muscle fiber (muscle cell). It plays a critical role in muscle excitation and contraction.

Structure of the Sarcolemma

The sarcolemma consists of two primary layers:

• Inner Layer (Plasmalemma): This is the true cell membrane, a lipid bilayer. It is excitable, meaning it can generate and propagate action potentials. Invaginations of the plasmalemma form transverse tubules (T-tubules), which are crucial for transmitting the action potential deep into the muscle fiber.
• Outer Layer (Basement Membrane): This extracellular layer surrounds the plasmalemma and is composed of several sub-layers:
  • Basal Lamina: An internal layer, further divided into:
    • Lamina Lucida: A clear, deep layer.
    • Lamina Densa: A dense layer.
  • Reticular Lamina: An external layer containing collagen fibers, which provide structural protection and help attach muscle fibers to one another and to connective tissue.

Functions of the Sarcolemma

The sarcolemma performs several vital functions in muscle physiology:

• Anchoring: It provides attachment points for the endomysium (connective tissue surrounding individual muscle fibers), motor neurons, and tendons, integrating the muscle fiber into the larger muscle structure.
• Muscle Fiber Regeneration: It plays a role in the repair and regeneration of damaged muscle fibers.
• Neuromuscular Transmission: It forms the motor end plate, facilitating communication between motor neurons and muscle fibers.
• Enzymatic Activity: It contains acetylcholinesterase (AChE), an enzyme that rapidly breaks down acetylcholine (ACh) in the synaptic cleft, ensuring precise control over muscle contraction.

Myofibrils: Muscle Contraction Units

Myofibrils are long, cylindrical organelles that make up the bulk of a muscle fiber. They are responsible for muscle contraction and are characterized by their distinctive pattern of alternating dark (A) bands and light (I) bands, which give skeletal muscle its striated appearance.

Sarcomere: The Contractile Unit

The sarcomere is the fundamental contractile unit of a myofibril. It is defined as the region between two successive Z-lines (or Z-discs). Each sarcomere contains an organized arrangement of two main types of protein filaments:

• Thick Filaments: Primarily composed of the protein myosin.
• Thin Filaments: Primarily composed of actin, tropomyosin, and troponin.

Thick Filaments (Myosin)

Thick filaments are composed mainly of myosin proteins. Each myosin molecule has a complex structure:

• Heavy Chains: Two heavy chains form the long tail and two globular heads. The heads contain actin-binding sites and ATPase activity.
• Light Chains: Four light chains are associated with the myosin heads. These include two essential light chains and two regulatory light chains, which modulate myosin head activity.

Titin: The Elastic Protein

Titin is a giant, elastic protein with a complex structure. It is embedded in the Z-line and extends along the thick filaments towards the M-line. At its ends, titin has a spring-like shape. This elasticity is crucial because titin contributes to the passive elasticity of muscle, helping to increase muscle contraction strength after a maximum stretch and facilitating the recovery of the muscle's initial form after contraction or stretching.

Thin Filaments (Actin, Tropomyosin, Troponin)

Thin filaments are composed of three main proteins:

• Actin: A globular protein (G-actin) that polymerizes to form filamentous actin (F-actin), which appears as a double helix. Each G-actin molecule possesses an active site where myosin heads can bind.
• Tropomyosin: A filamentous protein that, in a relaxed muscle, lies along the actin filament and covers the active sites on approximately seven G-actin molecules, preventing myosin binding.
• Troponin: A complex of three distinct subunits, each with a specific role in muscle contraction:
  • Troponin I (Inhibitory): Binds to actin, inhibiting the interaction between actin and myosin.
  • Troponin C (Calcium-binding): Binds with calcium ions (Ca2+), initiating the conformational changes that lead to muscle contraction.
  • Troponin T (Tropomyosin-binding): Forms an intimate relationship with tropomyosin, linking the troponin complex to the tropomyosin molecule.

Sarcoplasmic Reticulum: Calcium Storage and Release

The sarcoplasmic reticulum (SR) is a specialized type of endoplasmic reticulum found in muscle cells (sarcoplasm). It forms an intricate network of interconnected tubules and cisternae that surround each myofibril, playing a crucial role in regulating intracellular calcium levels, which is essential for muscle contraction and relaxation.

Key Components of the Sarcoplasmic Reticulum

• Terminal Cisternae: These are enlarged, sac-like regions of the sarcoplasmic reticulum located on both sides of each Z-line. They serve as the primary storage sites for calcium ions (Ca2+) within the muscle fiber. The terminal cisternae are characterized by the presence of ryanodine receptors (RyR), which are calcium release channels.
• Longitudinal Sarcoplasmic Reticulum: This network of tubules connects the terminal cisternae. The longitudinal SR is rich in calcium pumps (SERCA pumps), which actively transport Ca2+ from the sarcoplasm back into the SR lumen, facilitating muscle relaxation.

Transverse (T) Tubules and the Triad

While structurally distinct from the sarcoplasmic reticulum, Transverse (T) Tubules are intimately associated with it and are vital for muscle excitation-contraction coupling. T-tubules are deep invaginations of the sarcolemma (the muscle cell membrane) that penetrate into the interior of the muscle fiber. They surround the myofibrils at the level of the Z-lines (or A-I band junction in some muscles).

A single T-tubule is typically flanked by two terminal cisternae of the sarcoplasmic reticulum. This structural arrangement forms a functional unit known as a triad. The close proximity of the T-tubule membrane and the SR membrane allows for rapid communication, ensuring that the action potential propagating along the sarcolemma is quickly transmitted to the SR, triggering calcium release and initiating muscle contraction.