Neuromuscular junctions and motor units

Question 1

Learning outcomes

Answer 1

• Explain the three levels of integration of motor control
• Outline the release mechanism of acetylcholine, with particular emphasis on the role of calcium ions in triggering this
• Describe the functional properties of the postsynaptic (muscle) receptor and ion channel, and describe how acetylcholine produces a depolarisation in the muscle fibre, meaning that one action potential in a nerve always gives rise to one twitch in a muscle fibre
• Outline how the process referred to above may be manipulated pharmacologically and by disease processes.
• To characterise the motor unit (defined as one motor neurone and all of the muscle fibres it innervates) as the basic unit of motor control

Question 2

Levels of integration

Answer 2

Cortical level- The highest level of neural activity
Science, philosophy, art

Subcortical level:Primitive actions-Securing food and water, Reproduction

Spinal cord level: Homeostasis, reflex actionsThe simplest level of neural activity, Stereotyped behaviour

Question 3

Neuromuscular junctions

Answer 3

Nerve signals –Muscle AP’s
•Myelin sheath lost
•Boutons terminating in Motor End Plate
•Junctional folds- that contain:
•Vesicles and Nicotinic Ach receptors 

•Structure of ACH

Question 4

Neuromuscular transmission

Answer 4

Impulse arrival opens Ca++ channels
•Exocytosis of clear Ach vesicles into the cleft
•Nicotinic Ach Receptors (15-40 X 10^6 per synapse)
•Open cation (Na+, Ca++, K+) channels
•End plate potential
At rest, quantal release 0.5 mV
•Miniature End Plate Potential (MEPP)
•Arrival of impulse, MEPP’s ^ size
•Temporal summation, firing level; EPP –Action potential
•Similar to generator potentials in sensory physiology •1 impulse, 60 X 10000 molecules, 10 times required. APs in muscle often set up

Question 5

Excitation- contraction coupling

Answer 5

AP’s on sarcolemma
•Conducted in by T-tubules
•Voltage gated Ca++channels lining T-tubules
•Coupled with ryanodine receptors on SR
•Release Ca++intracellularly 
•Contraction
•Calcium pump limits contraction

Question 6

Termination of acetylcholine action

Answer 6

1. Acetylcholine diffuses out of the synaptic cleft (a small amount)
2. Acetylcholine is destroyed by acetylcholinesterase which hydrolyses it into choline and acetate

Result: acetylcholine persists in the synaptic cleft only for a few milliseconds
But:Nerve ending has enough acetylcholine vesicles only for ~3,000 discharges
Acetylcholine has to be constantly replenished
Choline is taken up by the nerve ending and used for acetylcholine synthesis