Muscular System

Contraction Skeletal Muscle Cell / Muscle Fiber

• Under voluntary control by lower motor neuron of the somatic nervous system

• Lower motor neurons = neurons from brain stem and spinal cord that synapse directly with skeletal muscle fibers

• Upper motor neurons = neurons that originate from the cortex

  • synapse indirectly

  • mainly inhibitory synapses

    • Disinhibition if UMN is damaged

• Nicotinic receptors are sodium channels

  • When ACh binds ( ligand ) they open

• Acetylcholinesterase is needed for ACh reuptake

  • Serin gas poisoning blocks acetylcholinesterase

    • $\therefore$$\therefore$ muscles never relax

      • $\therefore$$\therefore$ suffocation

Neuromuscular Junction

• Chemical synapse between lower motor neuron and muscle fiber

• Sarcolemma at the neuromuscular junction know as the motor end plate

  • Extensively folded ( increases surface area )

    • Allows for an increased number of nicotinic receptors

Excitation - Contraction Coupling

• Process by which muscle fiber excitation causes muscle fiber contraction

• Lower motor neuron releases ACh

  • Diffuses across the synaptic cleft to the motor end plate

• ACh binds to nicotinic receptors on the motor end plate

  • Nicotinic receptors open and transport sodium across sarcolemma

    • Causes a depolarization

• Action potential generated if threshold is reached ( EXCITATION )

• Continuous conduction of action potentials along sarcolemma and T-tubules

• Opens calcium channels of the terminal cisternae

  • Stored calcium within sarcoplasmic reticulum is released

    • Calcium diffuses to myofibrils

• Calcium binds to troponin

  • Causes a conformation change in troponin

• Troponin pulls on tropomyosin

  • Reveals active sites ( sites where myosin heads attach ) on actin

• Myosin heads attach to active sites on actin ( cross-bridge )

  • Phosphate that is attached to myosin head is released

• Myosin heads "ratchet" ( power-stroke ) medially

  • ADP that is attached to myosin head is released

• Thin filaments slide medially over thick filaments ( sliding filament model )

  • Sarcomeres shorten , which shortens muscle fiber ( CONTRACTION )

• New ATP binds to myosin head , which causes myosin head to release actin

  • ATP is hydrolyzed and myosin head is once again in a high energy state and ready to attach to active sites on actin again
  • Myosin heads split the ATP into an ADP and single Phosphate

• Thin filaments slide laterally over thick filament

  • Sarcomeres lengthen to original position ( RELAXATION ) ( slides laterally )

• Meanwhile

  • Released $C{a}^{2+}$$Ca^{2+}$ is transported into the sarcoplasmic reticulum via $C{a}^{2+}$$Ca^{2+}$ pumps

  • ACh is broken down into acetic acid and choline by acetylcholinesterase

    • Reuptake of choline by the lower motor neuron that released it

      • Choline used by lower motor neuron to produce new ACh

• Excitation - Contraction Coupling continues until action potentials stop

Length - Tension Relationship of Individual Muscle Fiber

• Relationship between sarcomere length and tension produced during contraction

• Sarcomere length of $2.0$$2.0$ to $2.25$$2.25$ $\mu m$$\mu m$ = optimal length

  • Generates the greatest amount of tension
  • Allows for the maximum number of cross-bridges
  • Distance the thin filaments slide is at a maximum

• Sarcomere length greater than $2.25\mu m$$2.25\ \mu m$

  • Muscle was overstretched

  • Tension generated is reduced

  • Number of cross-bridges that can be formed is reduced

    • Therefore the distance the thin filaments slide is reduced

• Sarcomere length less than $2.0\mu m$$2.0\ \mu m$

  • Tension generated is reduced
  • Distance the thin filaments can slide is reduced

Twitch - 1 Muscle Fiber

• Contraction and relaxation of one muscle fiber due to a single stimulus

• Lag Phase

  • Time between stimulus and beginning of a contraction
  • Generation of action potential to formation of cross-bridge

• Contraction Phase

  • Time during which contraction occurs
  • Power stroke causing the sliding of thin filament medially

• Relaxation Phase

  • Time during which relaxation occurs
  • ATP binding myosin head to sliding of thin filament laterally
  • All $C{a}^{2+}$$Ca^{2+}$ has ben transported back into SR by $C{a}^{2+}$$Ca^{2+}$ pumps

• Contraction causes tension to be generated

• Tension is the same regardless of the stimulus magnitude ( all or none )

  • Stimulus either causes an action potential or it does not

    • If action potential is present , SR $C{a}^{2+}$$Ca^{2+}$ is released
    • If action potential is absent , SR $C{a}^{2+}$$Ca^{2+}$ is NOT released

Multiple-Wave Summation / Temporal Summation

• Increasing the stimulus frequency ( not magnitude ) :

  • Increases tension
  • Lag phase and relaxation phase get shorter
  • Contraction phase gets longer

• Calcium continues to be released with each successive stimulus

  • Myofibrils continue to be activated

• If you can keep calcium on troponin for a longer period of time , you can contract the muscle more.

Tetanus

• Constant contraction due to constant stimulation of muscle cell

• If you don't stop stimulating the muscle , it can't relax

• Continues release of calcium via $C{a}^{2+}$$Ca^{2+}$ channels

• $C{a}^{2+}$$Ca^{2+}$ pumps cannot transport $C{a}^{2+}$$Ca^{2+}$ fast enough

  • Ion pumps are slower than channels

• Calcium activates myofibrils continuously

  • Tension is constant and at a maximum

Twitch - Whole Muscle

• Twitch = contraction followed by relaxation

• Single contraction of a whole muscle in response to a single stimulus

  • Tension generated by activating motor units

Motor Unit

• Motor Unit = LMN + "N" number of muscle cells it inervates

• Axon of a single motor neuron and the muscle fibers it innervates

• Fewer muscle fibers in a motor unit allows for finer movements

  • eg , intrinsic hand muscles

• Greater muscle fibers in a motor unit in slow reacting muscles

  • eg , postural muscles ( leg , back muscles)

• Size of the motor unit $\propto$$\propto$ amount of contraction

Multiple Motor Unit Summation / Spatial Summation

• Increasing the size of the stimulus increases tension in the muscle

  • Activates an increasing number of motor units

• Subthreshold Stimulus = no motor units activated

  • Therefore no tension generated

• Threshold Stimulus = activates one motor unit

  • The least amount of tension is generated
  • NOT enough to cause movement

• Submaximal Stimulus = greater than threshold stimulus but less than maximal stimulus

  • Activates many motor units and thus generates greater tension
  • Where we are most of the time

• Maximal Stimulus = activates all motor units

  • Therefore generates maximum tension

• Supramaximal Stimulus = greater than maximal stimulus

  • No more motor units to activate

    • Tension does not increase further

Two Main Types of Muscle Contraction

• Isotonic

  • Contraction in which muscle length changes ( ie , shortens or lengthens )

  • Concentric = contraction while a muscle is shortening ( sarcomere shortens )

    • Muscle tension exceeds resistance and thus the muscle shortens

  • Eccentric = contraction while a muscle is lengthening ( sarcomere lengthens )

    • Resistance exceeds muscle tension and thus the muscle lengthens
    • "harder" on muscles than concentric

• Isometric

  • Transfer of force
  • Tension = Resistance = NO movement
  • Contraction while muscle length does not change ( sarcomere shortens though )
  • Muscle tension equals or does not exceed resistance
  • Pushing against an immovable object

• Isotonic and Isometric contractions often work together for many movements

  • eg , walking , going up and down stairs

Muscle Tone

• State of partial muscle contraction due to continuous stimulation of some motor units

  • Stimulation is minimal and does NOT cause contractions that elicits movement.

• Muscles are always slightly contracted

  • ACh is always being released in some amount

    • Submaximal , because stimulating more than 1 axon

• Keeps muscles ready for work ( ready for contraction )

• NOT to be confused with "toning" of muscles with exercise

• Decreased muscle tone with lower motor neuron dysfunction and myopathies

  • eg , due to neuropathies , myopathies , motor neuron disease , muscle weakness

• Increased muscle tone with upper motor neuron disfunction

  • over excite the muscle

  • eg , due to stroke , multiple sclerosis , motor neuron disease , cerebral palsy

    • "brisk reflexes" = opposite of diminished

• Scale = $[0,5]$$[\ 0\ ,\ 5\ ]$ , where $2^{+}$$2^+$ = normal

Muscle Cramps

• Involuntary and forcible contraction of muscle with failure to relax

• Most common causes :

  • Fatigue ( low ATP )

    • ATP-Calcium pumps turn off , therefore calcium is higher in sarcoplasm
    • Myosin heads also need ATP to let go of actin

  • Dehydration ( causes electrolyte and fluid imbalances )

    • changes membrane potentials

  • Low potassium , but not as often as one might think

Rigor Mortis

• State of constant muscle contraction that occurs several hours after death

  • Due to the complete depletion of ATP

    • Depletion of ATP does not allow myosin heads to release actin

Energy for Muscle Contraction

• Sources of ATP

  • Creatine Phosphate / Phosphocreatine

    • Organic , nitrogenous molecule produced by the liver and kidneys
    • Stored in muscle

  • Glucose

    • Stored as glycogen in muscle
    • Used during anaerobic and aerobic cellular respiration

  • Fatty Acids

    • Used during aerobic cellular respiration
    • Preferentially utilized at rest ( spares glucose )

  • Ketones

    • Converted into acetyl-CoA
    • Used during aerobic cellular respiration

  • Amino Acids

    • Utilized when glucose , fatty acids and ketones are not readily available
    • Used during aerobic cellular respiration

• Processes that Yield ATP

  • Phosphagen System

    • Phosphocreatine donates a phosphate to ADP to produce ATP

    • Very rapid production of ATP

      • Fastest of all the methods

    • ATP yield is very low ( 1 phosphocreatine yields 1 ATP )

    • Provides approximately 15 seconds of energy

    • Utilized ONLY during very intense events

  • Anaerobic Respiration

    • Preferred process for short , intense events
    • Rapid production of ATP
    • ATP yield is low ( 1 glucose yields 2 ATP )
    • Provides approximately 90 seconds of energy

  • Aerobic Respiration

    • Preferred processes if activity is prolonged

    • Yields a tremendous amount of ATP

      • Provides an "unlimited" amount of energy

    • Glucose , fatty acids , ketones , or amino acids can be used

Causes of Muscle Fatigue

• Metabolic Fatigue

  • Depletion of ATP

  • Accumulation of potassium outside of the muscle fiber

    • Because action potentials cause $K^{+}$$K^+$ to exit the cell

  • Accumulation of phosphate inside of the muscle fiber

    • Myosin head and cross-bridge formation hydrolyses ATP into ADP and phosphate

  • Accumulation of acid inside of the muscle

    • lactate , pyruvate , $C{O}_2$$CO_2$

• Psychological Fatigue

  • You "think" your muscles are fatigued ( not as fatigued as is perceived )

  • Signaling molecules produced during physical exertion

    • Signal the brain to cause muscles to feel tired

      • Defense mechanism to conserve energy

• Synaptic Fatigue

  • Depletion of ACh at the neuromuscular junction

    • Can occur during prolonged , intense exercise ( very rare )

  • Dysfunction at the neuromuscular junction

    • eg , myesthenia gravis

      • Autoimmune destruction of nicotinic receptors ( skeletal muscle )

    • eg , Lambert-Eaton myasthenia syndrome

      • Autoimmune destruction of presynaptic calcium channels

        • Decreased release of ACh

          • Rare , typically in cancer patients

Muscle Fiber Types

• Red , slow twitch fibers ( Type I )

  • Fatigue resistant ( slow oxidative )

    • High concentration of mitochondria

    • High concentration of myoglobin

      • Red , pigmented oxygen-binding protein
      • Similar to hemoglobin , just specific to muscle and carries less oxygen

    • More ATP produced aerobically

  • Contract relatively slowly

    • Slower myosin cross-bridge cycling and slower ATPase activity

  • Relax relatively slowly

    • Slower $C{a}^{2+}$$Ca^{2+}$ pumps

  • Suited for endurance

    • Fatigue resistant
    • Lots of oxygen and mitochondria for aerobic respiration

• White , fast twitch fibers ( Type IIx ) ( x = human )

  • High concentration of glycogen ( fast glycolytic )

  • Very low concentration of myoglobin $\therefore$$\therefore$ white in color

  • More ATP produced anaerobically and via the phosphogen system

  • Contract relatively rapidly

    • Faster myosin cross-bridge cycling and faster ATPase activity

  • Relax relatively rapidly

    • Faster $C{a}^{2+}$$Ca^{2+}$ pumps

  • Suited for explosive movements

    • NOT fatigue resistant

• Intermediate fibers ( Type IIa )

  • Fast twitch and fatigue resistant ( fast oxidative - glycolytic )
  • Not quite as resistant to fatigue as Type I fibers
  • Contract and relax nearly as quickly as Type IIb fibers
  • Color = pinkish , not as much myoglobin

Cardiac Muscle

• Involuntary

• Coupled via intercalated disks

  • Cross-bands that contain gap junctions interconnecting cardiac muscle fibers

    • Cardiac muscle forms a functional syncytium ( sheet ) ( electrically coupled )

      • Allows for coordinated excitation and contraction

• Striated ( myofibrils arranged like skeletal muscle )

• Large T-tubules ( larger than those of skeletal muscle )

• Well-developed sarcoplasmic reticula

• Calcium used for contraction is intracellular but "triggered" by extracellular calcium

  • Trigger calcium comes from cardiac muscle action potentials
  • Calcium released from sarcoplasmic reticulum

• Contractile mechanism is similar to skeletal muscle sliding filament mechanism

Smooth Muscle

• Involuntary

• Very small in comparison

• Two types of smooth muscle arrangement

  • Single-Unit / Unitary / Visceral

    • Most common type of smooth muscle arrangement

    • Coupled via gap junctions and thus form a functional syncytium

      • Allows for coordinated excitation and contraction

    • eg , found in the walls of the digestive tract , blood vessels , ureters , and uterus

  • Multiunit

    • Less well-organized and function independently of each other
    • eg , arrector pili and found in the iris and walls of some small blood vessels

• Myofibrils more randomly organized ( monkaHmm ) and thus , smooth muscle is not striated

  • Sliding of actin over myosin causes muscle fiber to shorten ( and thus contract )
  • Contain the calcium binding protein , calmodulin ( smooth muscle lacks troponin )

• Lack T-tubules

• Sarcoplasmic reticula not well developed

• Calcium used for contraction is both extracellular and intracellular

  • Most calcium released from calcium channels of the sarcolemma ( ie , extracellular )
  • Very little calcium comes from sarcoplasmic reticula ( ie , intracellular )