Lecture 9 - Drugs and synaptic transmission

Question 1

Synaptic transmission (9)

Answer 1

AP reach end of presynaptic neurone.
Depolarisation causes calcium channels to open, these diffuse into the presynaptic knob.
Synaptic vesicles fuse with presynaptic membrane and release neurotransmitters into synaptic cleft via exocytosis.
ACh binds to receptor sites on sodium ion channels in post-synaptic membrane.
Products are taken back into presynaptic knob.
ACh is broken down by an enzyme (acetylcholinerase).
Once transmitter has been terminated it can:
Be taken up into other cells
Taken back into terminal (recycled)
Metabolised by something outside of the cell.

Question 2

Sodium channel blockers (1)

Answer 2

Lignocaine, blocks nerve impulses (can’t flow).

Question 3

Calcium channel blockers (2)

Answer 3

w-conotoxin analogue.

Ziconotide.

Question 4

Vesicular release (7)

Answer 4

• Vesicular release: In our nerve cells we have proteins, SNARE.
• SNARE proteins come in two forms v (vesicular)-SNARE, t (terminal)- SNARE found in the membrane of the nerve.
• v-SNARE two main types - VAMP or Synaptobrevin.
• t-SNARES - Syntaxin-1, SNAP 25.
• v-SNARE and t- SNARE join together forming a SNARE pin. Calcium binds to synaptotagmin which stabilises the SNARE pin and causes the membrane to kink (banana shape) so the contents can leave.
• Botulism or Tetanus chomp the SNARE proteins in our cholinergic nerves. Toxins made of two parts, one which binds to a choline transporter, allowing the degradative part to enter the cell which can degrade one of the v/t-SNAREs.
• β bungarotoxin is a snake toxin commonly found in Malaysia.

Question 5

SNARE (1)

Answer 5

soluble N-ethylmaleimide-sensitive factor attachment protein receptor.

Question 6

Botulism (6)

Answer 6

Toxin produced by anaerobic bacterium Clostridium botulinum.
Very potent.
Minimum lethal dose in mice is 10^-12 g.
Similar to diptheria and tetanus toxins.
2 subunits:
1) Binds to a glycoprotein to CHOLINERGIC NEURONS allowing toxin entry.
2) Produces cellular effects (e.g. cleaves VAMP/Synaptobrevin etc).
Toxin is destroyed by heating to more than 85 degrees for longer than 5 minutes.

Question 7

Cholinergic neuron (3)

Answer 7

Uptake of precursors such as choline for ACh, the enzyme used is choline acetyl transferase.
Block our Na+ channels. Directly inhibit the choline uptake with HEMICHOLINUM. Prevent ACh storage in vesicles with vesamicol. Toxins halt affect the vesicular fusion process e.g. botulism toxin, snake one, tetanus toxin.
Cholinesterase inhibitors - will raise ACh levels in the vicinity of the receptor.

Question 8

Adrenergic neuron (3)

Answer 8

• Sympathetic nerves release noradrenaline. It has a precursor molecule tyrosine. NA is packaged in vesicles and tends to be stored with a co-transmitter ATP.
• Noradrenaline made in steps. (Step 1- rate limiting step).
• NA is taken up into the cell metabolised (does not have to be degraded by an enzyme like ACh). Can be repackaged or can be metabolised by a monoamine transporter.