Muscle Physiology: Calcium's Role

• Lecture 19 covers muscle physiology I.
• The suggested reading for this lecture is textbook pages 198-206.

Ca+2 physiology

• Calcium (Ca2+) has an important role in muscle physiology.

The Importance of Calcium

• In mammals, 99% of calcium is stored in the skeleton and teeth.
• Only free Ca2+ in plasma is biologically active and subject to regulation.
• Ca2+ homeostasis and balance must be regulated.
• Calcitonin and PTH have a key role in calcium regulation.
• Calcium plays roles in neuromuscular excitability, the nervous system, excitation-contraction coupling in cardiac and smooth muscle, stimulus-secretion coupling, maintenance of tight junctions between cells, and blood clotting.

Muscle Cells

• Muscle cells are specialized to produce force and do work.
• Muscle cells utilize a highly developed microfilament system.
• The sarcomere is the basic functional unit of muscle tissue.
• Sarcomeres are composed of actin and myosin fibers.
• Muscle cells can shorten and develop tension.
• Muscle cells convert the chemical energy of ATP into mechanical energy.
• There are three types of muscle cells: skeletal, cardiac, and smooth.
• Contraction of muscles permits purposeful locomotory movement, manipulation of external objects, propulsion of contents through hollow internal organs and emptying the contents of certain organs into the external environment.
• Muscle contractions also facilitate the production of heat and sound.

Classification of Muscle Tissue

• Functional classification includes skeletal, cardiac, and smooth muscle.
• Innervation can be voluntary or involuntary.
• Structural classification includes striated and unstriated muscle.
• Skeletal muscle is striated and voluntary.
• Cardiac muscle is striated and involuntary.
• Smooth muscle is unstriated and involuntary.

Skeletal Muscle

• Makes up the muscular system.
• Skeletal muscle cells (muscle fibers) are large, elongated, cylindrical cells with a diameter of 10-100 μm.
• Skeletal muscle cells are formed by the fusion of many myoblasts during embryonic development and have multiple nuclei.
• Muscle fibers lie parallel to each other and are bundled together by connective tissue.
• Skeletal muscle cells extend the full length of the muscle.

Myofibrils

• Myofibrils are lines of sarcomeres.
• Myofibrils are specialized contractile elements.
• Myofibrils typically make up 90% of muscle volume.
• Myofibrils are cylindrical intracellular organelles, approximately 1 μm in diameter, extending the entire length of the muscle fiber.
• The greater the density of myofibrils, the greater the force that can be generated.
• Muscle fibers with a low percentage of myofibrils cannot generate much tension but can contract at high frequency or for prolonged periods of time.
• Myofibrils have a regular arrangement of thick and thin filaments.

Thick Filaments

• Thick filaments are 12-18 nm in diameter and 1.6 μm in length.
• Myosin is the contractile protein that composes thick filaments.
• Myosin tails are intertwined with globular heads projecting out at one end.
• Each globular head has an actin binding site and an ATPase.

Thin Filaments

• Thin filaments are 5-8 nm in diameter and 1.0 μm in length.
• Actin is the contractile protein that composes thin filaments.
• Thin filaments have sites for attachment to myosin.
• Tropomyosin forms strands that cover actin binding sites when muscle is relaxed.
• Troponin is a protein complex with three subunits.
• One troponin subunit binds to tropomyosin, one binds to actin, and one can bind with Ca2+.
• When troponin is not bound to Ca2+, it stabilizes tropomyosin in its blocking position.

Basis of Striations in Skeletal Muscle

• Striations are due to alternating dark bands, or A bands, and light bands, or I bands.
• The A band includes stacked thick filaments, as well as portions of overlapping thin filaments.
• The H zone, the lighter area in the middle of the A band, contains only thick filaments, with no overlapping thin filaments.
• The M line is located in the center of the A band and holds thick filaments together.
• The I band consists of thin filaments where they do not overlap with thick filaments.
• The Z line, found in the center of the I band, is a flat cytoskeletal disc that connects thin filaments.
• The sarcomere, the functional unit of skeletal muscle, is the area between two Z lines and is 2.5 μm in width.

Skeletal Muscle Fiber Types

• These include slow-oxidative fibers (Type I), fast-oxidative fibers (Type IIa), and fast-glycolytic fibers (Type IIb, IId, or IIx).

Slow-Oxidative Fibers (Type I)

• Develop peak tension in 60-100 msec.
• Exhibit lower myosin-ATPase activity.
• Primarily rely on aerobic metabolism, making them more resistant to fatigue.
• Show high resistance to fatigue.
• Smaller in diameter compared to Type II fibers.
• Appear darker under a microscope due to a higher content of myoglobin and mitochondria.
• Richly supplied with capillaries, enhancing oxygen delivery.
• Ideal for endurance, aerobic exercises, and sustained activities (posture).

Fast-Oxidative Fibers (Type IIa)

• Develop peak tension in 20-40 msec.
• Exhibit higher myosin-ATPase activity.
• Show intermediate resistance to fatigue.
• Utilize both aerobic and anaerobic metabolism.
• Larger in diameter compared to Type I fibers.
• Have fewer capillaries compared to Type I fibers.
• Appear lighter under a microscope because they have less myoglobin and fewer mitochondria.
• Generate moderate force.
• Have fast contraction speed.
• Well-suited for activities requiring both endurance and power, such as middle-distance running and swimming.

Fast-Glycolytic Fibers (Type IIb, IId, or IIx)

• Similar to fast-oxidative fibers in speed and myosin-ATPase activity.
• Exhibit low resistance to fatigue and tire quickly.
• Larger in diameter compared to Type I fibers.
• Fewer capillaries compared to Type I fibers.
• Primarily rely on anaerobic metabolism.
• Generate high force.
• Very fast contraction speed.
• Ideal for short, explosive movements like sprinting and weightlifting.

Adaptation of Muscle Fibers

• Skeletal muscle has a high degree of plasticity.
• Regular endurance activities improve oxidative capacity.
• This occurs through an increase in the number of mitochondria and capillaries.
• Regular high-intensity activity stimulates hypertrophy (increased diameter) of fast-glycolytic fibers.
• Hypertrophy results from increased synthesis of myosin and actin filaments, ultimately increasing muscle strength.
• Hormones influence muscle size and strength.
• Testosterone and growth hormone/IGF-I promote the synthesis of myosin and actin filaments.
• Myostatin (GDF-8) is a negative regulator of muscle growth, inhibiting muscle from growing excessively and secreted by muscle cells.
• Interconversion between fast-glycolytic and fast-oxidative fibers takes place with specific forms of regular exercise.
• Unused muscle loses mass and strength (disuse atrophy).
• When muscle is damaged, repair is limited by the ability to form myoblasts, which originate from satellite cells (stem cells in skeletal tissue).

Smooth Muscle

• Mostly in the walls of hollow organs and tubes.
• Fibers are smaller than skeletal muscle fibers and spindle-shaped, with a single nucleus.
• Fibers are arranged in sheets.
• There are three types of filaments.
• Thick myosin filaments.
• Thin actin filaments are anchored at dense bodies.
• Intermediate filaments form a scaffold for dense bodies.
• It has a diagonal arrangement of filaments resulting in no visible striations.
• Smooth muscle is regulated by the autonomic nervous system.

Classification of Smooth Muscle

• Phasic smooth muscle contracts in bursts triggered by action potentials that cause increased cytosolic Ca2+.
• Tonic smooth muscle is partially contracted at all times and varies its contraction according to cytosolic Ca2+ level. i.e., sphincters

Cardiac Muscle

• Only found in the heart.
• Cardiac muscle cells are called cardiomyocytes.
• Regulated by the autonomic nervous system.
• Cardiomyocytes can generate their own electrical impulses, allowing the heart to beat independently of nervous system input.
• Rich in mitochondria.
• Shows visible striations and has thick and thin filaments.
• Cells adhere to each other by the intercalated disc, which facilitates transmission of nerve impulses (gap junctions).

Next Class

• Review slides of Muscle physiology II and muscle contraction physiology.
• Suggested reading textbook p 206-216.