Chapter 9 – MUSCLE TISSUE Structure, Function & Metabolism Alireza Ashraf, M.D. Associate Professor of Physical Medicine & Rehabilitation Shiraz Medical school

Summary General Types of muscle tissue Functional characteristics Functions Structural organization of skeletal muscle Gross and microscopic anatomy Excitation/contraction sequence Muscle metabolism

General Skeletal muscle represents about 40% of our body mass, including smooth and cardiac muscle the figure may be as high as 50% Muscles transform chemical energy into mechanical energy, i.e. exert a force. Muscles pull they do not push. Skeletal and smooth muscle cells are called fibers. Myo-, mys- and sarco- refer to muscles

Types of Muscle Tissue, Table 9.3 Skeletal Smooth

Types of Muscle Tissue Cardiac

Functional Characteristics Excitability (irritability) – receive and respond to stimuli. Stimuli = neurotransmitters, extracellular pH Response = generation of an electrical impulse (AP) Contractility = ability to shorten, requires energy Extensibility = ability to stretch, does not require energy Elasticity = ability to recoil, i.e. return to resting length

Functions of Muscle Tissue Produces movement Locomotion Propulsion Manipulation Maintains posture Stabilizes joints Generates heat – primarily skeletal m.

Structural Organization of Skeletal Muscle, Table 9.1 Fascicles = Cell = Myofibrils Myofilaments

Skeletal Muscle Gross Anatomy Tissues: Blood vessels Nerves – branches to each fiber Connective Tissue (Fig 9.2, Table 9.1) Endomysium –wraps each fiber Perimysium –wraps fibers into fascicles Epimysium –wraps fascicles into a muscle All are continuous with each other and the tendons.

Skeletal Muscle Microscopic Anatomy, fig 9.3 Cell membrane = sarcolemma Cell interior gel = sarcoplasm with myoglobin Organelles Mitochondria, multiple nuclei, etc. squeezed between myofibrils. Myofibrils aligned in such a way as to produce alternating light (I) and dark (A) bands or striations.

Skeletal Muscle Microscopic Anatomy

Skeletal Muscle Microscopic Anatomy Myofibrils – hundreds to thousands per cell contain the contractile proteins = myofilaments Actin – thin filaments Myosin – thick filaments

Skeletal Muscle Microscopic Anatomy Bands A bands = actin & myosin overlap I bands = actin only H zone in A band – myosin only Z disc – attachment of actin and myosin; distance between Z discs = sarcomere

Skeletal Muscle Microscopic Anatomy Closer look at a sarcomere

Skeletal Muscle Microscopic Anatomy Ultrastructure of Sarcomere, fig 9.4 Myosin – 2 globular heads whose tails are intertwined. Heads are the “business” end, i.e. form cross bridges with actin. Actin – globular proteins arranged like 2 strands of beads twisted together in a helix. Tropomyosin – protein filaments give strength and cover active sites on actin. Troponin – controls position of tropomyosin.

Skeletal Muscle Microscopic Anatomy Sarcoplasmic reticulum – smooth ER, regulates intracellular calcium; forms paired terminal cisternae at A-I junctions. T-tubules – invaginations of sarcolemma that reach each A and I band junction, traveling between paired terminal cisternae = triad. Communicate with external environment, carry electrical impulses into muscle mass.

Skeletal Muscle

Contraction – Sliding Filament Model Sliding filament theory Hugh Huxley 1950’s Contraction (shortening) - the thin filaments slide past the thick filaments and overlap increases. Relaxation (lengthening) - thin filaments return to their original position. Occurs simultaneously in sarcomeres throughout the fiber = muscle shortening.

Physiology of Skeletal Muscle Fiber Neuromuscular junction – chemical synapse (Fig 9.7)

Physiology of Skeletal Muscle Fiber Neural Stimulation Motor neuron generates electrical impulse (AP) that travels down the axon to the synapse. The impulse opens Ca2+ channels, Ca2+ moves in and causes vesicles, filled with ACh, to empty the ACh into the synaptic cleft. ACh diffuses across the cleft to the Motor End Plate on the muscle fiber and binds to ACh receptors. Acetylcholinesterase destroys remaining ACh quickly to confine stimulation locally.

Neuromuscular Junction

Physiology of Skeletal Muscle Fiber Skeletal Muscle Excitation, fig 9.8 Sarcolemma is polarized at rest, inside negative relative to the outside. RMP = -65mV ACh binds to ACh receptors at motor end plate and opens LG Na+ channels, Na ions move into the cell causing a small depolarization.

Physiology of Skeletal Muscle Fiber Excitation cont’d At threshold potential, VG Na+ channels open. Na+ rushes into the cell and an Action Potential is generated.

Physiology of Skeletal Muscle Fiber Excitation cont’d AP is propagated along entire sarcolemma. Repolarization follows closely behind depolarization as Na channels close and VG K channels open to restore the membrane potential back to normal. During this period, the muscle fiber cannot produce another action potential = Refractory Period.

Contraction Sequence, fig 9.10 Latent Period (excitation/contraction coupling) Action potential (AP) travels across sarcolemma down the T-tubules to Terminal Cisternae. Terminal Cisternae – Ca2+ channels open and release stored Ca2+ into sarcoplasm.

Contraction Sequence Contraction Ca2+ binds to troponin that then pulls tropomyosin out of groove to expose the active sites on actin. As calcium levels increase, the myosin heads are activated and alternately attach/detach from actin filaments, moving them toward the center of the sarcomere. The sarcomere shortens.

Contraction Relaxation Ca-ATPase (calcium pump) moves calcium back into the terminal cisternae, tropomyosin moves back to cover active sites on actin. Myosin heads detach and actin filaments move back to resting position = relaxation

Contraction Role of ATP: Cross-bridge formation: ATPase on head hydrolyses ATP to ADP and Pi and head “cocks” to attach to actin. Power stroke: head rotates downward and pulls actin toward center of sarcomere, ADP and Pi are released Cross bridge detachment – head binds a new ATP

Contraction

Muscle Metabolism Stored ATP – 4-6 seconds but is regenerated by 3 mechanisms: Direct phosphorylation of ADP from creatine phosphate (CP) with the help of creatine kinase. SUPER FAST gives another 6-10 seconds of activity. Anaerobic glycolysis – glucose is broken down into 2 pyruvate molecules and 2 ATP molecules. Fast but short term – supports another 30-40 seconds of activity. Problem - lactic acid build-up

Muscle Metabolism Energy Aerobic glycolysis (respiration) or Kreb’s Cycle Glucose + O2 yields CO2 + H2 O + 30 ATP’s Pyruvate, amino acids, and fatty acids can also enter this cycle. Slow process, more useful for endurance exercise.

Fatigue Physiological inability of a muscle to contract – not enough ATP; different from psychological fatigue. ATP production lags behind use – contractures (no ATP to release cross bridges. Accumulation of lactic acid decreases pH and inhibits ATP production. Restoration of ionic balance of Na and K requires ATP also – impaired with intense exercise.

Fatigue Prolonged exercise leads to SR damage and lack of control of intracellular Ca. Oxygen debt = amount of oxygen needed to restore muscle anaerobic fuel stores.

Heat 60% of the energy released by muscle contraction is in the form of heat – 40% is in the form of work. Shivering is muscle contraction used to warm a cold body. When you exercise strenuously your body heats up. How is the heat dissipated?????