Neuromuscular transmission

Question 1

Describe components of neuromuscular junction.

Answer 1

• transmission of impulses from nerve cells to skeletal muscle fibers unidirectionally.
• motor unit
• presynaptic side
• synaptic cleft
• post synaptic side

Question 2

What is a motor unit?

Answer 2

• consists of a motor neuron and the muscle fibers that innervates
• different muscles have different sized motor units that relate to their function

Question 3

Describe role of acetylcholine in neuromuscular transmission.

Answer 3

• diffuses across synaptic cleft and binds w/ transmitter specific receptors in postsynaptic membrane
• binds to nicotinic acetylcholine receptors
• channels open for specific ions
  –> Na flows inside cell
  –>locally depols muscle fiber membrane
  —–> END PLATE POTENTIAL = increases in positive direction 50 - 75 mV
• ACh is rapidly removed from synaptic cleft
  1. a few msecs after release most of ACh is destroyed by enzyme Achetylcholinesterase
  *choline is transported back into presynaptic terminal - recycled
  *acetic acid + choline
  2. small amounts diffuses out of cleft and no longer available
  —>prevents continuous muscle re-excitation

Question 4

Describe how neuromuscular transmission occurs.

Answer 4

1. AP is release and reached neuromuscular junction
2. ACh is released from terminals into synaptic space
3. a wave of depol opens VOLTAGE GATED CALCIUM CHANNELS
4. calcium enters presynaptic terminal
5. raise in Ca releases vesicles from site
6. vesicles move to active zone
   –>dock, fuse and release ACh by exocytosis
7. each diffuses across synaptic cleft and binds w/ transmitter specific receptors in postsynaptic membrane
8. attaches to nicotinic ACh receptors, opening channels
9. Na flows into cell and locally depols membrane
10. ACh is removed from synaptic cleft
11. ACh gets recycles back into pre synaptic cleft

Question 5

What is botulinum toxin?

Answer 5

• toxin usually ingested from uncooked/spoiled food
• prevents the release of ACh from vesicles ( and autonomic synapse )
  -causes flaccid muscle paralysis
  –> progressive motor paralysis
  –> disturbed vision
  –> difficulty chewing and swallowing
  –> generalised and progressive paresis
  –> death occurs due to respiratory/cardiac paralysis

Question 6

What is organophosphate carbamate pesticides?

Answer 6

• major cause of animal poisoning
  –> used as insecticides/pesticides
• inhibits ACh enzyme
• shows signs of cholinergic ACh overstimulation
  –>nicotinic = muscle fasciculations and weakness
  –>muscarinic =
  *hyper salivation
  *meiosis
  *frequent urination
  *diarrhea
  *vomiting
  *colic
  *dyspnea
  –>central =
  *nervousness
  *ataxia
  *apprehension
  *seizures

Question 7

What is myasthenia gravis? How does it influence in NMJ?

Answer 7

• disease caused by abnormal reduction in # of ACh receptors on neuromuscular endplate
  –> congenital form = present from birth
  *recurrent and progressive muscle fatigue usually becomes apparent between 6-9 weeks
• can be linked to problems in ACh synthesis
  –>Acquired form = autoimmune disease IgG against ACh receptors
  *ABs may bind directly to ACh receptor blocking ion channels opening
  *ABs may increase degradation rate of ACh receptors resulting in decreased conc. of receptors at postsynaptic membrane
  *complement mediated lysis of muscle endplate complication

Question 8

Describe how excitation contraction coupling occur.

Answer 8

• transformation of nerve impulse into muscle contractions
• AP in muscle fibers will occur in same way as nerve cells
• AP on sarcolemma spread in both directions along length of fiber
• also spread to interior of cell along transverse tubules
• In SR, AP causes conformational change in voltage sensing receptors
  –> leading to open of Ca+ release channels in terminal cistern of SR
  –> Ca rapidly diffuses out of SR and initiates contraction
• Ca+ pump removes Ca ions from myofibril fluid after contraction occurs
  –> located in walls of SR and pumps Ca in
  –> muscle contraction continues as long as Ca ion conc. remain high