BIOSCI 107: Excitable Tissue: Muscle Flashcards

Excitable Tissue: Muscle - Lecture Notes

Introduction

• Associate Professor Carolyn Barrett (c.barrett@auckland.ac.nz) - Department of Physiology, Faculty of Medical and Health Sciences.
• Research focuses on blood pressure control and cardiovascular disease, particularly preeclampsia.
• This lecture series will cover skeletal, cardiac, and smooth muscle.

Learning Objectives

• Describe the structure and organization of skeletal muscle.
• Describe the structure of thick and thin filaments in skeletal muscle.
• Describe the events during the cross-bridge contraction cycle.
• Describe the role of calcium in muscle contraction.
• Describe the length-tension relationship in skeletal muscle.

Types of Muscle

1. Skeletal Muscle:
   • Attached to bones, responsible for movement.
   • Voluntary control via the somatic nervous system.
   • Striated appearance due to highly ordered contractile system.
   • Long, cylindrical cells with multiple peripheral nuclei.
2. Cardiac Muscle:
   • Forms the bulk of the heart mass, ejects blood via contraction.
   • Involuntary control via the autonomic nervous system.
   • Striated appearance.
   • Located only in the heart.
   • Branched cells with 1-3 central nuclei.
   • Connected via intercalated discs.
3. Smooth Muscle:
   • Lines hollow organs and blood vessels, regulates their dimensions.
   • Involuntary control via the autonomic nervous system.
   • Not striated.
   • Found in the walls of internal organs (gut, blood vessels, etc.).
   • Spindle-shaped, uninucleated cells.

Muscle Classification

• Striated Muscle: Skeletal and cardiac muscle, characterized by a highly ordered contractile system giving a banded appearance under a light microscope with a periodicity of about 2 \mu m.
• Voluntary Muscle: Skeletal muscle, under conscious control for limb movement.
• Involuntary Muscle: Cardiac and smooth muscle. Cardiac muscle pumps blood, while smooth muscle alters the dimensions of blood vessels and hollow organs. May have intrinsic contractile activity (myogenic) modulated by the nervous system, or be initiated by autonomic nervous system input.

General Organization

• Muscle cells are interconnected via direct cellular contacts (common in cardiac muscle) or innervation by the same neuron (skeletal and most smooth muscles).
• Interconnections allow coordinated activity.
• A motor unit is a group of muscle cells innervated by a single neuron.
• Actin and myosin are the main proteins responsible for contraction.

Structure of Skeletal Muscle

• Highly ordered structure.
• Cells are long (up to several cm) and wide (about 0.1 mm), referred to as muscle fibers.
• Attached to tendons, which attach to bones.
• Contractile apparatus is organized into fibrils running the length of the cell.

Myofibrils

• Composed of alternating bands of actin (thin) and myosin (thick) filaments, which interdigitate.
• Sarcoplasmic Reticulum (SR): Extensive membrane-bound compartment surrounding the fibril, serving as a calcium store that releases calcium to activate contraction.
• Sarcomere: Basic contractile element consisting of thick (myosin) and thin (actin) filaments attached to Z-discs at each end.
• T-tubules: Invaginations of the sarcolemma (surface membrane) at the junction between A and I bands, allowing action potentials to be carried deep within the muscle cell.
• Sarcomeres are surrounded by the SR, with terminal cisterns closely apposed to the T-tubules.

Sarcomere Structure

• I band: Contains only thin filaments.
• A band: Contains thick filaments and overlapping thin filaments.
• Z disc: Anchors thin filaments and connects myofibrils to one another.
• H zone: Lighter mid-region where filaments do not overlap.
• M line: Holds adjacent thick filaments together.

Filament Structure

Thin (Actin) Filaments

• Composed of globular actin proteins.
• Attached to the Z line at either end of the sarcomere.
• Actinin interconnects thin filaments at the Z line.
• Four main proteins: F-actin, nebulin, tropomyosin, and troponin.
• Accessory proteins (troponin and tropomyosin) regulate activity.

Thick (Myosin) Filaments

• High molecular weight protein with two heavy chain subunits.
• Each subunit has a tail (double helix) and a globular head that hydrolyzes ATP.
• Light chains (accessory proteins) regulate the catalytic ability of myosin to hydrolyze ATP.
• Myosin molecules are polarized along the filament.
• A typical thick filament contains approximately 300 myosin molecules.
• Heads have a binding site for actin.
• Titin anchors the thick filament to the Z-line.

Sliding Filament Model of Contraction

• Contraction is the activation of myosin cross-bridges.
• Thin filaments are pulled over thick filaments, shortening the sarcomere.
• Z-discs are pulled toward the M-line.
• I band and H zone become narrower.
• A bands do not change in length.

Chemical Basis of Contraction

• Myosin heads are ATPases, hydrolyzing ATP to ADP and Pi.
• The conformation of the myosin head depends on whether ATP or hydrolyzed ATP (ADP + Pi) is bound.
• Flexibility resides in the ‘hinge’ region near the globular head.
• Actin binding promotes ATP hydrolysis, causing myosin to take on a new conformation.
• Relative motion between actin and myosin filaments occurs as myosin heads swing.
• If motion is prevented, force is produced between the filaments.
• Rebinding of fresh ATP allows detachment and return to the original conformation.

Cross-Bridge Cycle

1. Energization: ATP binds and hydrolyzes to form myosin-ADP-Pi complex (high affinity for actin).
2. Crossbridge Formation: Myosin-ADP-Pi binds to actin in a 90^o orientation.
3. Power Stroke: Release of ADP-Pi results in a minimum free energy at about 45^o orientation.
4. Detachment: ATP binding reduces myosin's affinity for actin, leading to detachment. Absence of ATP leads to rigor (rigor mortis).

Regulation of Contraction by Calcium

• Calcium ions act as an ‘on switch’ for contraction.
• Interact with troponin (actin-regulated muscles) or calmodulin (myosin-regulated muscles).
• Muscle is relaxed at calcium levels less than 0.0001 mM and activated at 0.001 – 0.01 mM.
• Calcium source: outside the cell and/or release from the sarcoplasmic reticulum.
• Transient changes in calcium (calcium transient) activate muscle cells.
• Opening calcium ion channels increases myoplasmic calcium levels.
• In skeletal muscle, opening of calcium channels in the SR allows calcium ions to move into the cytosol.
• Active transport pumps (Ca2+ ATPase) constantly move Ca2+ from the cytoplasm back into the sarcoplasmic reticulum.
• Removal of calcium from the cytoplasm is an active process linked to ATP hydrolysis by ion pumps in the surface membrane.
• Relaxation occurs when calcium influx channels close and pumps return calcium to stores and/or extracellular space.
• The New River Water Company contains 278.6 parts of solids per million, including Calcium (38.3) and Magnesium (4.5).

Role of Troponin and Tropomyosin

• When calcium binds with troponin, tropomyosin moves to expose myosin binding sites on actin.
• The cross-bridge cycle continues as long as calcium levels remain above the critical threshold (0.001-0.01 mM).

Length-Tension Relationship

• The amount of overlap between thick and thin filaments determines the number of attached cross-bridges.
• Maximal overlap at a sarcomere length of 2.0 – 2.2 \mu m (2.0 – 2.2 x 10^{-6} m).
• Injuries may increase the possible range of sarcomere lengths.
  • At lengths < 2.0 \mu m, active force development reduces due to filament collision.
  • At lengths > 2.2 \mu m, passive force increases due to stretching of elastic connective tissue and cytoskeleton.
• Active force declines as filament overlap reduces.
• Maximal force develops between 2.0 – 2.2 \mu m, the normal working range of the muscle.

Types of Contraction

• Isometric Contraction: Muscle develops force without shortening (length constant, tension variable).
• Isotonic Contraction: Muscle shortens with constant tension (tension constant, velocity variable).