Skeletal Muscle Thought Questions Answers

• 1. h. Actin
• 2. e. Myosin
• 3. b. T-tubule
• 4. b. T-tubule
• 5. d. Sarcoplasmic reticulum
• 6. f. Troponin
• 7. g. Tropomyosin
• 8. c. ATP

Muscle

• Almost all cells have intracellular machinery for movement
• The contraction specialists of the body are muscle cells
• Skeletal
• Cardiac
• Smooth Muscle Cells
• Skeletal muscle fibers have a highly developed ability to contract, develop tension, and do work.

Contraction of Muscle Allows

• Purposeful movement of the body in relation to the environment
• Manipulation of external objects
• Propulsion of contents through hollow organs
• Emptying the contents of organs to the environment

Muscle Composition

• Muscle comprises the largest group of tissues in the body
• ~ 40% body weight in men, ~32% in women
• Skeletal muscle: 660 in the adult human
• Smooth and Heart = 10%

Muscle Classification

• Functional vs Structural
• Skeletal Muscle - Voluntary
• Cardiac Muscle - Involuntary
• Smooth Muscle - Involuntary

Organization of the Nervous System

• The nervous system is comprised of the central nervous system (CNS) and the peripheral nervous system (PNS)
• The CNS includes the brain and spinal cord.
• The PNS consists of all the nerve fibers branching out from the CNS, connecting it to the rest of the body, transmitting sensory stimuli.
• Different divisions branch out from the CNS and PNS to control different functions, and effector organs will carry out orders.

Levels of Organization in Skeletal Muscle

• Whole muscle = an organ
• Muscle fiber = a cell
• Relatively large (up to 2.5 ft)
• Multinucleated to maintain high protein production
• Myofibril = intracellular structure
• Thick and thin filaments = myofilaments
• Myosin and actin = contractile proteins

Contractile Proteins

• Thick filaments: several hundred myosin (heads and tails)

Thin Filaments

• Mostly actin (helix)
• Regulatory proteins: tropomyosin and troponin

Changes in Banding Pattern During Shortening

• Light microscope: light and dark bands
• Relaxed: H zone, I band, A band
• Contracted: H zone shorter, I band shorter, A band same width
• Sarcomere shorter

Medical Mnemonic

• Muscle sarcomere: Only one vowel in dark and light (dark = A band, light = I band)
• Muscle sarcomere bands: "Zee Intelligent Animal Has Muscle" (ZIAHM) --> From the Z line working inward (ZIAHM)

Questions

• Which of the following is the light band of the sarcomere?

• I band

• Which of the following remains the same width during contraction?

• A band

• Which of the following describes a sarcomere?

• All of the above

Molecular Basis of Muscle Contraction

• Resting State: Ca2+ absent in sarcoplasm; SERCA actively pumps Ca2+ into the SR; no attachment between actin & myosin filaments; muscle cell is relaxed

Excitation-Contraction Coupling

• Excitation of Muscle Cell: Propagated action potential; Acetylcholine is released in the cleft; Acetylcholine binds to receptors on the motor end plate; cation channels open; Na+ moves in EPP
• The Result of Excitation: Specialized membranes take AP from the surface to the center of the cell; SR = modified ER, consists of interconnecting tubules surrounding each myofibril. T-tubule runs perpendicular to surface.

Excitation-Contraction Coupling: Spread of AP down T-tubules, activates receptors, DHP receptor, voltage-gated Ca2+ channel.

Excitation-Contraction Coupling: Steric Block Model

• Ca2+ binds to troponin
• Troponin changes its shape
• Troponin-tropomyosin complex is physically pulled aside
• Actin's binding sites uncovered

Excitation-Contraction Coupling: Cross-bridge Cycling

• Before X-bridge ever links: ATP hydrolyzed; ATP and P remain attached to myosin; Energy stored in X-bridge (“cocked” and ready to be fired). Steps: Energized, Resting, Binding, Bending, Detachment

Excitation-Contraction Coupling – Cross-bridge Cycling (Continued)

• Binding of fresh ATP breaks linkage between actin and myosin

Which is responsible for removing the steric inhibition for the act of contraction?

• Ca2+

Which is responsible for detachment?

• ATP

Excitation-Contraction Coupling – Return to Resting State

• Neural excitation stops: - Acetylcholine released by axon of motor neuron crosses cleft and binds to receptors on motor end plate
• Previously released ACh is broken down by AChase
• SERCA pumps Ca2+ back
• Dihydropyridine channels close; diffusion of Ca2+ out of SR stops
• Actin's binding sites are covered; actin slides back to relaxed position away from center of sarcomere

All of the following result in muscle relaxation EXCEPT:

• No more ATP or Rigor Mortis

Agents & Diseases that Affect the NMJ

• Alters the Release of ACh: Black widow spider venom, Clostridium botulinum toxin
• Blocks ACh Receptor: Curare, Myasthenia Gravis
• Prevents Inactivation of ACh: Organophosphates (certain pesticides and nerve gases)

Synapse vs NMJ

• Similarities: 2 excitable cells separated by a narrow cleft; axon terminals store NT released by Ca2+ induced exocytosis; NT binds to receptors on the membrane, which open channels
• Differences: Synapse – junction between 2 neurons, NMJ – junction between a motor neuron and a skeletal muscle fiber; NMJ is always excitatory (EPP); Synapse is excitatory (EPSP) or inhibitory (IPSP)

Skeletal Muscle has 3 Energy Systems

• 1. Immediate: ATP and CP, available immediately to drive muscle contraction
• 2. Nonoxidative: breakdown of glucose and glycogen
• 3. Oxidative: breakdown of carbohydrates, fats, & certain amino acids

Muscle Fiber Types

• Based on: Speed of contraction (myosin ATPase activity), Type of metabolic pathway
• Type I: slow twitch, slow oxidative (ST), SO
• Type IIa: fast twitch, fast oxidative/glycolytic (FOG), FTa
• Type IIx: fast twitch, fast glycolytic (FG), FTx

Type I vs Type II

• Type I: Slow twitch, oxidative metabolism, ~50% of fibers, used for endurance-type activities, Soleus muscle
• Type II: Fast twitch, Type IIa: moderate high ox capacity, high glycolytic capacity, ~25% fibers, used for higher intensity movements
• Type IIx: low ox capacity, highest glycolytic capacity ~25% fibers, used for explosive movements

Motor Units

• Motor unit = 1 motor neuron + all the muscle fibers it innervates
• When a motor neuron is activated, all fibers it supplies contract simultaneously
• For stronger contractions, more motor units are recruited

Motor Unit Recruitment

• Method for altering force production: Less force production - smaller motor units (type I); More force production - larger motor units (type II)

Size Principle of Motor Neuron Recruitment

• The CNS increases muscle force by activating additional motor units in the order of their increasing size, starting with the smallest. Recruitment order: type I, type Ila, type IIx

Increased use: strength training

• Neural adaptations must take place before changes in muscle size
• Early gains in strength due to neural factors. Later, increasing cross-sectional area (hypertrophy) becomes more important

Skeletal Muscle Mechanics: contraction of whole muscles

• The force exerted by the same muscle can vary depending on the load.
• Examples: piece of paper, book, 50lb weight

Two major factors determine gradation of whole muscle tension

• The # of muscle fibers contracting within a muscle

  • of motor units recruited; Size of the motor unit

• The tension developed by each contracting fiber
  • Frequency of stimulation; Length-tension relationship

Frequency of Stimulation

• Twitch summation: fiber stimulated a second time before it relaxes = greater tension
• Tetanus: fiber stimulated so rapidly no relaxation

Length of Muscle fiber

• Length-tension relationship: The relationship between initial length and tension can be explained by the # of cross-bridges that can be formed during the contraction
• Tension is greatest when the muscle is at a certain length; too short or too long cause less force, as the availability of overlapping myofilaments is less.

Muscle Contraction Types

• Isometric: Muscle produces force but does not change length; Joint angle does not change
• Isotonic: Muscle produces force and changes length; Joint movement produced

Isotonic Contraction Subtypes:

• Concentric: Muscle shortens while producing force; Sarcomere shortens
• Eccentric: Muscle lengthens while producing force; Cross-bridges form, but sarcomere lengthens

Smooth Muscle

• Location: Walls of hollow organs (gallbladder, uterus, bladder); Tubes (GI tract, blood vessels)
• Characteristics: tone (basal tension); contractions superimposed on tone; maintains shape and pushes contents along.
• Contraction: Slower & longer; Generates comparable force using less ATP; Responds to variety of stimuli like nerves, hormones, stretch ; latch state is possible allowing prolonged contraction w/o input of ATP
• Structure compared to skeletal muscle: lacks sarcomeres (no striations), troponin, and t-tubules; has dense bodies (analogous to Z lines), dense bodies anchor actin, held in place by intermediate filaments; tropomyosin, but role unclear; caveolae: indentations in sarcolemma, may act like T tubules, SR but not well developed.
• Excitation-Contraction Coupling: RMP is relatively low (-50 to -60 mV), long AP = 10-50 ms (vs 2-3 ms in sk muscle); No voltage-gated Na+ channels
• Ca2+ triggers contraction: Role of Ca2+: The state of the thick filaments(not thin filaments) are affected by Ca2+. Where the Ca2+ comes from: Depolarization leads to voltage-gated Ca2+ channel opening. NTs, hormones can also open Ca2+ channels; some SR release

Smooth Muscle Contraction Mechanism

• Extracellular Ca2+ enters: Voltage-gated and ligand-gated channels; Stretch-activated channel
• Chemical activation: Ca2+ binds to calmodulin, leading to activation of myosin light chain kinase (MLCK); MLCK phosphorylates the light chain of myosin; when myosin is phosphorylated, X-bridges can form and break repeatedly. Smooth: myosin is “off”; Skeletal: myosin always “on”

Smooth Muscle Relaxation Mechanism

• Relaxation of smooth muscle is a result of removal of the contractile stimulus (↓ed [Ca2+]) or direct action of a substance that inhibits the contractile mechanism (↑ed myosin phosphatase activity)

Pharmacological Relaxation of Smooth Muscle

• L-type Ca2+ channel blocker ↑ in cAMP or cGMP; cAMP (EPI via β₂) inhibits MLCK; cGMP (nitroglycerin) stimulates myosin phosphatase

Tonic Contraction

• How can vascular smooth muscle (think aorta) endure 60 “insults” per minute & sustain BP w/o expending a lot of ATP?
• Smooth muscle has a way for cross bridges to remain attached, cycle slowly, & consume less ATP