Smooth & skeletal

Types of Muscle

• Skeletal muscle
  • Attaches to bones
  • Makes up 40% of body weight
  • Responsible for movement, facial expressions, posture, respiration, and other body movements
  • Voluntary movement; controlled by somatic motor neurons
• Smooth muscle
  • Found in walls of hollow organs, blood vessels, eyes, glands, uterus, and skin
  • Some functions include: moving urine, mixing food, dilating/constricting pupils, and regulating blood flow
  • Involuntary movement; controlled by endocrine and autonomic nervous systems
• Cardiac muscle
  • Found in the heart
  • Involuntary movement
  • Controlled by endocrine and autonomic nervous systems

Muscle Properties

• Excitability: Ability to respond to a stimulus
• Contractility: Ability to shorten and generate pulling force
• Extensibility: Ability to be stretched back to its original length
• Elasticity: Ability to recoil to its original resting length after being stretched

Muscle System Functions

• Body movement (locomotion)
• Maintenance of posture
• Respiration (diaphragm and intercostal contractions)
• Communication (verbal and facial expressions)
• Contraction of organs and blood vessels (e.g., peristalsis of intestines)
• Heartbeat
• Production of body heat (thermogenesis)

Skeletal Muscle Structure

• Muscle fibers: Basic cellular unit, the sarcomere
  • Muscle tissue made of fascicles, bundles of muscle cells, which are themselves bundles of myofibrils
• Nuclei: Multiple, located at the periphery of the cell
• Sarcolemma: Tubular sheath that encases and defines each muscle fiber, containing locations for ion exchange
• T-tubules: Invaginations within the sarcolemma
• Sarcoplasm: Cytoplasm of a muscle fiber, containing sarcoplasmic reticulum, mitochondria, glycogen, and ions
• Myofibrils: Structural components within muscle fibers, containing actin and myosin filaments

Organization of Skeletal Muscle

• Skeletal muscle is composed of muscle fascicles
• Fascicles are comprised of individual muscle fibers
• Fibers are further subdivided into sarcolemma, t tubules, sarcoplasm , sarcoplasmic reticulum and myofibrils
  • Myofibrils are composed of organized proteins, such as actin and myosin.
• These proteins organize into sarcomeres, the functional units of muscle contraction

Function of Skeletal Muscle

• Movement: Converts chemical energy to mechanical energy, generating force and power
• Body posture and position
• Storage of nutrients: Important for basal energy metabolism
• Maintenance of body temperature: Produced by muscular activity

Myofibrils

• Actin ("thin fibers"): Double-helical structure with polarized fibers; tropomyosin-troponin complex regulates interaction with myosin heads
• Myosin ("thick fibers"): Light meromyosin anchors myosin at the M line; heavy meromyosin S-1 portion (myosin head) binds actin, contains ATP sites, and initiates power stroke
• Supporting proteins: Titin, desmin, myomesin, C protein, nebulin, and plectin

Sarcomere

• Structural and functional unit of actin-myosin-linked muscle contraction
• Longitudinally arranged
• Include M line, Z discs, H band, A band, I band
• Z disc: Terminal boundary of the sarcomere
• I band: Contains only actin filaments
• A band: Contains the entirety of myosin and overlaps with actin
• H band: Contains only myosin filaments
• M line: Center of the sarcomere

Neuromuscular Junction

• Junction between motor neuron and skeletal muscle fiber
• Linked chemically
  • Neurotransmitter at junction: Acetylcholine (ACh)
• Axon approaches muscle: Dividing into terminal branches, losing myelin sheath
• Axon terminal branch: Enlarged knob-like structure called the terminal button with vesicles of chemical transmitter
• Motor end-plate: Specialized area of muscle fiber membrane invaginated by motor nerve terminal

Motor end-plate

• The axon terminal contains vesicles that hold acetylcholine (ACh)
•  Synaptic cleft: 20-30nm space separating the axon terminal and the muscle cell membrane
•  Synaptic trough (synaptic gutter): Muscle membrane containing many folds called subneural clefts, where Ach receptors are located

Events at the Neuromuscular Junction

• Action potential to axon terminal
• Release and diffusion of acetylcholine
• Binding of acetylcholine to receptors
• Opening of gated Na+ channels
• Na+ influx, triggering end-plate potential (EPP)
• EPP initiates action potential in muscle fiber
• Acetylcholine breakdown by acetylcholinesterase

End-plate Potential

• Influx of Na+ inside muscle fiber, provoking a local potential at end-plate
• Initiator of the action potential
• Threshold potential

Action Potential

• Skeletal muscle fibers: No current flow deep within the fiber
• T tubule-sarcoplasmic reticulum system: Transmits action potentials
• Transmission of action potentials along transverse tubules
• Open in the exterior of the fiber
• Sarcoplasmic reticulum vesicular tubules with high concentration of Calcium
• T tubule action potentials release of calcium—causing contraction of the muscle
  • Overall process called excitation-contraction coupling

Release of Ca2+ from the T-tubule sarcoplasmic reticulum system

• Action potential
• Dihydropyridine receptors (DHP receptors) sense voltage changes
• Pull the ryanodine receptor channels out in the sarcoplasmic reticular cisternae
• Calcium release causes contraction
• Calcium ions reuptake by calcium pumps (using ATP)

Cross-bridge Cycle

• Interaction between myosin heads and active sites on actin filaments
• Muscle relaxed: Low calcium, troponin-tropomyosin complex blocks actin sites
• Muscle contracted: Increased calcium, troponin-tropomyosin complex moves, exposing actin sites
• Myosin head attaches, moves, detaches, and reattaches
• Power stroke: Myosin head moves toward negative end of actin, pulling actin filaments
• Myosin detaches from actin: ATP binds to myosin
• Hydrolysis of ATP to ADP and Pi re-energizes the myosin head

Temporal Summation

• One action potential = one twitch (single muscle contraction)
• Amount of force produced very low
• Enhances contractile force: Repeated stimulation before muscle relaxes
  • Partially fused twitches
  • Tetanus

Pathophysiology of Neuromuscular Junction

• Disorders affecting neuromuscular junction, e.g.: Lambert-Eaton myasthenic syndrome (LEMS), Botulism, Myasthenia Gravis (MG)

Smooth Muscle

• Cells: Not striated, smaller than skeletal muscle cells, and usually cylindrical in shape; single nucleus; and lack striations or sarcomeres
• Caveolae: Indentations in the sarcolemma (may act like T tubules)
• Myofilaments: Thick myosin and thin filaments similar to actin, but lack troponin and tropomyosin
• Intermediate filaments: Cytoskeletal functions (non-contractile)
• Dense bodies: Membrane-associated structures instead of Z discs
• Group together into sheets in the walls of hollow organs
  • Longitudinal layer
  • Circular layer

Functions of Smooth Muscle

• Gastrointestinal tract: Propulsion of food,
• Cardiovascular: Regulation of blood flow,
• Renal: Regulation of urine flow,
• Genital: Muscle contractions during pregnancy, propulsion of sperm
• Respiratory: Regulation of bronchiole diameter
• Integument: Raises hairs with erector pili
• Sensory: Dilation and constriction of pupils, changing lens shape

Cell-to-cell Transmission and Electrical Activity in Smooth Muscle

• Single-unit: Often autorhythmic, and nerve innervations to cells are few. Coordinate contractions through electrical coupling via gap junctions
• Multi-unit: Each cell requires its own electrical impulse for activation (e.g., arrector pili muscles, large blood vessels, iris or eyes, airways)

Smooth Muscle Properties: Single Unit

• Gap junctions: Electrical coupling, potential change spreads to multiple cells
• Innervation: Primarily to few cells; coordinate contraction (e.g., GI tract)
• Slow, steady contractions, substance movement
• Tone: Basis level of contraction without stimulation
• Location: Walls of visceral organs (e.g., stomach, intestines, urinary bladder)

Smooth Muscle Properties: Multi-Unit

• No gap junctions
• More precise muscle control
• Produce asynchronous contractions
• Location: Large blood vessels, eyes, and respiratory airways

Direct and Receptor-Mediated Factors that Contract or Relax Smooth Muscle

• Direct Factors
  • Increase intracellular calcium = contraction
  • Passive diffusion of ligands to specific membrane receptors
• Receptor-Mediated Factors (chemical factors)
  • Chemical constrictors (e.g., noradrenaline) 　 - Relaxants (e.g., nitric oxide, CO2)

Contraction of Smooth Muscle

• Direct entry: passive calcium entry from leak channels, or voltage gated channels
• Second messenger system (IP3 induces release of calcium from sarcoplasmic reticulum)

Activation Cross-bridge Cycle in Smooth Muscle

• Lack troponin complex, regulated by myosin linked myosin
• Increased intracellular Ca2+ (depolarization activation, and/or Ca2+ release from SR)
• Calmodulin binds calcium
• Calcium-calmodulin complex activates myosin light-chain kinase (MLCK)
• MLCK phosphorylates light chains in myosin
• Increases myosin ATPase activity
• Myosin-P binds actin

Smooth Muscle Relaxation

• Reduces cytoplasmic calcium concentration (repolarization or calcium pump activity)
• Calcium unbinds from calmodulin
• Myosin light-chain phosphatase (MLCP) dephosphorylates myosin
• Dephosphorylated myosin: Low affinity for actin
• Cross-bridge cycle interruption = relaxation

Contractile Activity in Smooth Muscle

• Tonic contraction: Low, sustained tension. Ligan-gated calcium channels. Direct metabolic control.
• Phasic contraction: Momentary contraction with momentary activation of VG calcium channels. Similar to skeletal muscle twitch

Pathophysiology of Smooth Muscle

• Digestive system: Gastroparesis (loss of motility), Nerve dysfunction, collagen disease, muscular dystrophies
• Renal system: Chronic kidney disease (leads to end-stage renal disease), Ureters (nephrolithiasis), Bladde (neurogenic)
• Cardiovascular and respiratory systems: Atherosclerosis, pulmonary hypertension, asthma

Smooth, Skeletal, and Cardiac Muscle Comparison

• Properties like striations, level of control, neural input, hormonal control, calcium source, regulatory proteins, gap junctions, pacemaker activity, myosin ATPase, recruitment are compared