Pharmacology Flashcards
All skeletal muscle motorneurones are myelinated, T/F?
False - they are myelinated until they reach the muscle where they divide into unmyelinated branches
What are the “important” areas of the NMJ? (4)
1) Active Zone (presynaptic; ACh vesicles)
2) Synaptic Cleft
3) Sarcolemma of muscle containing nicotinic ACh receptors
4) End plate
ACh is made from which precursors
Choline + Acetyl CoA
Which enzyme synthesises ACh?
ChAT (choline acetyltransferase)
Which enzyme packages the ACh into vesicles?
Vesicular ACh transporter
An action potential causes which events in the pre-synaptic terminal/buton? (2)
Opening of calcium channels (voltage gated) allowing calcium into the cell + triggering exocytosis
What is the ACh receptor composed of?
5 M2 receptors arranged into a pore
What is the net effect on the post-synaptic muscle cell once ACh has bound?
ACh receptors open, allowing sodium in and potassium out. Net gain is depolarisation as more sodium flows in than potassium out.
What is an end-plate potential?
The potential of the muscle fibre once the ACh receptors have opened allowing depolarisation
What is the mepp?
Miniature end plate potential - the amount of electrical activity elicited by one quantum of neurotransmitter binding
In normal skeletal muscle, one AP triggers how many twitches?
1 (there is 1: 1 coupling)
Why are sodium channels required on the muscle fibre & why must these be open in contraction?
They continually refresh the AP, without them it would tail off
Skeletal muscle fibre is/ is not “all or none”?
It is (i.e. a threshold has to be reached to trigger contraction)
In muscle fibres, where does calcium come from? What is its purpose?
Exclusively from the SR (c.f. cardiac which gets it from ECM and SR) and enables coupling by interacting with troponin
Which enzyme terminates ACh signalling?
Acetylcholinesterase
Botulinum toxin is directed against what structure/function of skeletal contraction?
It blocks fusion of the ACh-filled vesicles with the membrane; preventing the presynaptic terminal from releasing them.
Myasthenia gravis is a muscle weakness driven by what pathophysiology?
Antibodies against the nicotinic ACh receptor
Neuromyotonia underlying pathophysiology
Antibodies against potassium channels (causes hyperexcitability / spasticity)
LEMS underlying pathophysiology
Antibodies against calcium channels on the neurone
Curare is a reversible/ irreversible receptor binder?
Reversible (used in surgery)
How does curare work?
Competitive antagonist of ACh receptor, reduces amplitude of epp and thus it will not reach threshold for contraction
Does botulinum cause reversible/ irreversible muscle paralysis?
Irreversible
On which membrane is acetylcholinesterase associated?
End-plate membrane
Acetylcholinesterase works slowly/quickly
Very quickly
