Physiology of the skeletal neuromuscular junction

Question 1

Skeletal fibres is innervated by motor neurones with _______ axons and cell bodies in the spinal cord or brain stem

Answer 1

Myelinated

Question 2

The motor neurone divides into _____ branches near to the muscle

Answer 2

Unmyelinated

Question 3

Each branch ends with a ________ _____ thats forms a chemical synapse with the muscle membrane at the neuromuscular junction

Answer 3

terminal bouton

Question 4

Where is ACh synthesised?

Answer 4

In the cytosol (from choline and acetyl coenzyme A)

Question 5

What glycoprotein subunits make up a nicotinic receptor?

Answer 5

a, a, b, d, e

e replaces y which is in the embryonic form

Question 6

The open channel is more permeable sodium T/F

Answer 6

F- the open channel is roughly equally permeable to Na+ and K+

Question 7

Because the driving force for Na+ is ______ than for K+ at resting membrane potential ____ for Na+is greater than ____ for K+; a depolarisation known as the end plate potential (e.p.p) is generated

Answer 7

Greater

influx

Efflux

Question 8

What is a miniature endplate potential ( m.e.p.p)

Answer 8

The electrical response to one quantum of transmitter, due to the activation of nicotinic Ach receptors at the endplate

Question 9

Many m.e.p.p summate to produce the e.p.p- a graded response. If this exceeds the threshold what happens?

Answer 9

an “all or none” propagated action potential that initiates contraction

Question 10

Normally one AP in the motor neurone triggers one AP in the muscle and a subsequent twitch of the muscle. T/F

Answer 10

T

Question 11

What are transverse T tubules?

Answer 11

Invaginations of the sarcolemma that dip deeply into the muscle cell

Question 12

What causes rapid termination of neuromuscular transmission?

Answer 12

Hydrolysis of Ach by acetylcholinesterase (AChE)

Question 13

AChE hydrolyses Ach to choline and acetate. What happens to them?

Answer 13

Choline- taken up by the choline transporter

Acetate- Diffuses from the synaptic cleft

Question 14

What is Neuromyotonia (NMT or Issac’s syndrome)

• Symptoms
• Cause
• Treatment

Answer 14

Symtoms inc multiple disorders of skeletal muscle- cramps, stiffness, slow relaxation (myotonia) and muscle twitches (fasciculations)

Autoimmune-antibodies against voltage-activated K+ channels in the motor neurone disrupt function resulting in hyper excitability (repetitive firing)

Drug treatment inc anti-convulsants (e.g. carbamazepine, phenytoin) which block voltage-activated Na+ channels

Question 15

Lambert-Eaton Myasthenic Syndrome (LEMS)

• Symtoms
• Cause
• Treatment

Answer 15

muscle weakness in the limbs- rare and associated with small cell carcinoma of the lung (may improve upon exertion)

Autoimmune-antibodies against voltage-activated Ca2+ channels in the motor neurone terminal result in reduced Ca2+ entry in response to depolarisation and reduced vascular release of Ach

Drug treatment-anticholinesterases (e.g. pyridostigmine) and potassium channel blockers (e.g. 3,4-diaminopyridine) which inc conc of Ach in synaptic clef

Question 16

Myasthenia Gravis (MG)

• Symptoms
• Cause
• Treatment

Answer 16

Progressively inc muscle weakness during periods of activity. Often weakness of the eye and eyelid muscle is a presenting feature

Autoimmune- antibodies against nicotinic Ach receptors result in reduction in number of functional channels and hence amplitude of e.p.p

Drug treatment- anticholinesterases ( edrophonium for diagnosis but pyridostigmine for long term treatment) and a variety of immunosuppressive agents (e.g. azathioprine). Anticholinesterase inc concentration of Ach in the synaptic cleft

Question 17

How does botulinum toxin work?

Answer 17

Enter presynaptic nerve terminal to enzymatically modify proteins involved in the docking of vesicles containing Ach (therefore blocking exocytosis). It irreversibly inhibits Ach release

Question 18

How do curare-like compounds work?

Answer 18

They interfere with the postsynaptic action of Ach by acting as competitive antagonists of the nicotinic Ach receptor ( e.g. vecuronium, atracurium)

they reduce the amplitude of the endplate potential (e.p.p) to below the threshold for muscle fibre action potential generation