Skeletal muscle

Question 1

What is the structure of skeletal muscle?

(see PP for diagram)

Answer 1

• Large cells extend the length of the muscle
• Multiple nuclei (fused smaller cells)
• No gap junctions
• Myosin and actin
• Actin connected to Z lines
• Troponin/tropomyosin complex
• Sliding filament applies to this and both smooth and cardiac muscle

Question 2

What is necessary for contraction of skeletal and caridac muscle?

Answer 2

• Skeletal muscle cells contain troponin C- tropomyosin complex
• Contraction dependent upon calcium binding to troponin C.
• Causes a conformational change which casues the troponin complex to move, allowing myosin to bind to the actin

Question 3

What are the innervation pathways for Skeletal muscle?

Answer 3

• Somatic
• Parasympathetic
• Sympathetic

Question 4

What is a “motor unit”?

Answer 4

• Single myelinated axon that can be 1 metre in length
• Branch close to their targets
• Allows 1 motor neurone to control many muscle fibres at 1 time
• Nerve fibre end in neuromuscular junction

Question 5

Explain diagram? (motor unit?)

Question 6

What factors affect force generation?

Answer 6

• Size (cross-sectional area)
• Freq of stimulation
• 1.Force of contraction inc with inc freq of APs
• Skeletal muscle cannot maintain tension (unlike sooth muscle)
• Over stimulation causes tetanus, over contraction of muscles, fatigues very quickly.

Question 7

How can you pharmacologically manipulate the NMJ?

Answer 7

• Neuromuscular blockade (paralysis/muscle relaxation)
  1. Acute procedures e.g. tracheal intubation, dislocations
  2. Surgery
  3. Cosmetic
  4. Movt disorders e.g. tics
• Augment function:
  1. Myaesthenia gravis (muscle weakness due to NKJ dysfunction)

Question 8

What can you target at the NMJ pharmacologically?

Answer 8

• Target synthesis of NTs
• Reuptake/inactivation of NTs
• The release of NTs
• Receptors NTs bind to

Question 9

What are the 2 classes of neuromucular blockers?

Answer 9

1. Non-depolarising
2. Depolarising

Question 10

What are Non-depolarising NM blockers?

Answer 10

• nACh-R antagonists e.g. atracurium, vecuronium
• Derived from: Tubocuraine-poison
• Blocks NM transmission-paralysis

Question 11

What are the features of non-depolarising blockers?

Answer 11

• Blocks post-synaptic nACh receptors
• Block is competitive
• Onset of action 3-5min, duration typically 30+min: suitable for surgery
• Block not preceded by stimulation ie. no contraction of muscle
• Block antagonised by agents that depolarise muscle membranes or inc ACh release
• Block reversed by anticholinesterase

Question 12

What are depolarising blocking drugs?

Answer 12

• nACh-R Agonists ie. mimic ACh/nicotine
• E.g. Suxamethonium, decamethonium

Question 13

What are the features of depolarising blockers?

Answer 13

• Persistent activation of nACh-R casues inactivation of voltage gated Na+ channels ie. can no longer open in response to brief depolarization
• Block preceded by muscle twitches

Question 14

What is BOTOX?

Answer 14

• Botulinum toxin type A
• blocks ACh releases – paralysis

Question 15

What is myaesthenia gravis?

Answer 15

• Autoimmune disorder of neuromusculr transmission
• Autoantibodies against the nicotinic AChR are detectable in the sera of 80-90% of patients with MG
• Muscle weakness
• Inability to prolong muscle contraction
• Ptosis(droopy upper eyelid)

Question 16

Treatment aims of myaesthenia gravis?

Answer 16

• Increase ACh in end plate
• Short acting: Anticholinesterase (diagnosis) e.g. edrophonium (Tensilon)
• Long acting: Anticholinesterase e.g. neostigmine,pyridostigmine