Topic 17 - The regulation of muscle work and muscle-nerve connection: the motor unit

Question 1

Words to include in the regulation of muscle work

Answer 1

• Neural activation
• Muscle contraction
• Action potential (AP)
• Motorneuron
• Myoneural junction
• ACh
• ACh-R
• Sarcolemma
• ACh channel
• Na⁺
• Ca²⁺
• Local end plate potential (Local EEP)
  
  • Local current
• Sarcoplasmic reticulum (SR)
• T-system
• Sarcoplasa
• Actin-myosin contraction
  
  • Sliding filament mechanism
• Mitochondrion
• Neuromuscular junction
  
  • Nerve terminal
  • Nicotinic receptors
  • Ligand activated cation channels
  • Voltage gated sodium channels
  • Conformation change
  • Myolemma
    
    • Muscle membrane
  • ACh (acetylcholine)
    
    • Golgi of motorneuron
    • Axon knob
    • Cytosol
    • Voltage gated calcium channels
    • Exocytosis
    • Synaptic space
    • Cholin esterase
      
      • Cholin
      • Acetat
    • ACh-receptor
• Neural signal (=AP)
• Electrical signal (=AP)
• Chemical signal (=ACh)
• Presynaptic area
• Synaptic cleft
• Postsynaptic area
• Neuromuscular transmission (→ drugs affecting)
  
  • Nicotine
  • Cholinesterase inactivators
  • Curaiform drugs
  • Pariesis
  • Myasthenia gravis
    
    • Autoimmune disesase
  • Myoneural junction
• Nicotinic acetylcholine receptor
  
  • Muscle type nicotinic ACh receptor
    
    • 2 alpha
    • 2 beta
    • 1 delta
  • Competitive blocking effect
    
    • Curare
    • Bungarotoxin
• Magnesium
  
  • Parturient paresis
  • Area uncer endplate
  • Normal myolemma
  • Muscle contraction (ø)

Question 2

Words to include in muscle-nerve connection: the motor unit

Answer 2

• Voluntary actions
• Involuntary actions
• Sensory side
• Receptor
• Effector
• Afferent nerve
• Efferent nerve
• Acting side
• Sensory side
• CNS
• Motor unit
  
  • Motor neuron
  • Skeletal muscle
  • Motor neuron’s axonal terminals
  • Large motor unit
    
    • Glycolytic
    • White phasic fiber
  • Small motor unit
    
    • Tonic
    • Red aerobic fibers
• Nerve
  
  • Diameter
  • Conduction
  • Stimulation
• Muscle
  
  • Fiber nuber
  • Diameter
  • Force
  • Metabolism
  • Speed
  • Fatigue
  • Length
• Muscle-nerve connection (morphology)
  
  • Neural arborizations
  • Nerve fiber:muscle ratio

Question 3

Give the steps from neural activation to muscle contraction

Answer 3

1. AP of a motoneuron is generated which runs to the myoneural junction
2. ACh containing vesicles open up at the synaptic knobs → ​ACh deliberation
3. ACh attached to ACh-R of sarcolemma → ACh channel opens
4. Na⁺ enters through the channels to inner surface
   
   • Local EPP (End Plate Potential) is generated → AP is generated
5. Spreading of AP (in Phasic muscle)
6. AP activates sarcoplasmic reticulum through T-system
   
   • Result: Ca²⁺ is released to the sarcoplasma
7. Ca²⁺ initiates Actin-Myosin contraction (sliding filament mechanism)
8. Repumping of Ca²⁺ into:
   
   • Sarcoplasmic reticulum
   • Mitochondrion
   • EC
9. Result: Leading to relaxation

Question 4

The neuromuscular junction

Answer 4

• AP is generated on the myolemma only if it is stimulated through a nerve
• The reason of this connection is the acetyl choline release
  
  • Induced by the AP at the nerve terminals
  • This chemical sign binds to the nicotinic receptors of the muscle membrane
    
    • ​Result: opening of ligand activated cationic channels
• The opening of these cationic channels produces a local current (end plate potential) which is gradually decreasing conducted to the fast, voltage gated Na⁺ channel situated next to the myoneural junction
  
  • There, a conformation change is induced and then AP is formed in the myolemma (muscle membrane)
• Acetylcholine is the neurotransmitter used at the neuromuscular junction
  
  • ​Motor neuronsof the neurous system releasesACh to activate muscles

Question 5

The neuromuscular junction

Acetylcholine

Answer 5

The life cycle of ACh in the neuromuscular junction:

1. Synthesis of empty vesicles in the Golgi of motor neuron
2. Flow of vesicles towards the axon knob
3. Local synthesis of ACh in the cytosol, immediate transport into empty vesicles
4. AP runs through the axon:
   
   1. Opens up the voltage gated Ca²⁺ channels
   2. Ca²⁺ influx from EC space increases Ca²⁺ concentration in the knob
   3. Exocytosis of ACh containing vesicle
5. ACh flows into the synaptic space → ACh binds to ACh-R →​ local end plate potential

The role of ACh:

• A neural signal is transformed to a muscular electrical signal (AP) by the mediation of a chemical signal (ACh)
• Presynaptic area:
  
  • ​APfromaxon
  • Neural AP induces Ca²⁺ entry to the synaptic ending
  • ACh vesicle release
• Synaptic cleft:
  
  • ​Filled with ACh
• Postsynaptic area
  
  • ​ACh binds to specific receptors on the myolemma
  • Ligand gated ion channels open:
    
    • Local end plate potential
  • End plate potential activates voltage gated Na⁺ channels
    
    • ​Formation and propagation of AP

Question 6

The neuromuscular junction

Nicotinic acetylcholine receptor

Answer 6

• N-ACh receptor is composed of the subunits:
  
  • 2 α
  • 2 β
  • 1 Δ
• The structure makes it possible to have competitive blocking of curare and bungarotoxin (poisons)

Role of magnesium:

• Increase in EC Mg²⁺ antagonize ACh receptor and blocks functioning of the sarcomere​
• Important in cattle: high Ca²⁺ secretion into the milk after calving decreases plasma calcium level:
  
  • Mg²⁺ concentration will not increase, but its higher proportion to Ca²⁺ results in the same effect as an absolute increase of the Mg²⁺ concentration
  • Muscles will relax: parturient paresis happens

Question 7

Drugs affecting neuromuscular transmission

Answer 7

1. Drugs of action similar to ACh
   
   1. ​Nicotine: Same effect like ACh, but can not be degraded by cholin esterase​
2. Cholinesterase inactivators
3. ​Curariform drugs
4. Blocking of ACh release
5. Myasthenia gravis
6. Fatigue of myoneural junction

Question 8

Motor unit

1. Composed of
2. Innervated by

Answer 8

1. Composed of: motor neurons and skeletal muscles
2. Innervated by: motor neuron’s axonal terminal

Question 9

Motor unit

• Give the division of the motor unit
• What are the differences between them?

Answer 9

Large motor unit

• Nerve:
  
  • Large diameter
  • Very fast conduction
  • Difficult stimulation
• Muscle:
  
  • Large fiber number
  • Large diameter
  • Large force
  • Anaerobic metabolism
  • Speed is fast
  • Easily fatigues
  • Fiber length is very long
• Glycolytic, white or phasic fiber

Small motor unit

• Nerve:
  
  • Small diameter
  • Fast conduction
  • Easy stimulation
• Muscle:
  
  • Few fiber number
  • Intermediate diameter
  • Small force
  • Oxidative metabolism
  • Slow speed
  • Ø fatigue
  • Fiber length is short
• Tonic, aerobic, or red fibers

Question 10

The fusimotor system

Answer 10

• Modified muscle fibers in skeletal muscles plays a role in:
  
  • Stretch-detection
  • Fine tuning of muscle tension
• The special fibers are named intrafusal fibers
  
  • ​Are located among working fibers named extrafusal fibers
• We can also find receptors in golgi tendon receptor organs

​Fusimotor system - afferentation:

• Static fibers are sensitive to static (length) changes of tension
• Dynamic fibers are sensitive to dynamic change of tension (length and velocity)

Question 11

Fine-tuning of muscle tension

Answer 11

• Muscle spindles is sensitive to stretching
• In case of the myotatic reflex, efferentation returns to the same muscle where the afferenteation (stretch of the muscle spindle) is coming from
• The reflex is monosynaptic due to the 1a afferentation directly activating to a large motorneuron (α-motorneuron) in the spnal chord

Responses:

1. Severo-mechanism:
   
   • ​The motor neuron stimulate the Aα- efferent, which runs to the extrafusal muscle → contraction, antigravitation
   • ​↑ stretching → ​↑ tension (contraction) in a monosynaptic way, without the influence of the cerebral motor center
2. Activation of the fusimotor system (𝝲-loop) - 1α-afferentation - also runs to the 𝝲-motorneuron, then 𝝲-efferent runs to the contractile part of the muscle spindle
   
   • Result:​ Stimulation of muscle spindle → fine adjustment of muscle tension
   • In this way, the system participates in the co-activation mechanism

Figure: severo-mechanism