Neurotransmitters and Pharmacology

Question 1

What is synaptic transmission?

Answer 1

Information transfer across the synapse requires the release of neurotransmitter and their interaction with postsynaptic receptor

1. Transmitter release from 1st cell
2. Synaptic activation of 2nd cell
3. Signal integration and signal conduction by 2nd cell
4. Signal transmitted to effectors or subsequent neurones

Question 2

How many synapses does each neurone recieve and make?

Answer 2

Several hundreds and thousands

Question 3

How large is the synaptic cleft?

Answer 3

about 20-100 nm

Question 4

What are examples of neurotransmitters?

Answer 4

Amino acids such as glutatamate, GABA, glycine

Amines e.g. noradrenaline and dopamine

Neuropeptides e.g. opioid peptides

Question 5

How many NT molecules are there per synaptic vesicle?

Answer 5

About 4000 - 10000

Question 6

How are NT’s released?

Answer 6

Ca2+ influx gives rise to docking (synaptic vesicles filled with NT)

Vesicles are docked onto presynaptic membrane and primed then undergo fusion

The vesicle then undergoes exocytosis

Empty vesicles bud off and are recyled- new vesicles formed

Question 7

What are vesicular proteins?

Answer 7

They’re targets for neurotoxins

Question 8

What are examples of neurotoxins?

Answer 8

Alpha latrotoxin (from black widow spider) stimulates transmitter release to depletion

Zn2+ dependent endopeptidases: inhibit NT release

Tetanus toxin (C tetani): causes spasms and paralysis

Botulinum toxin (c botulinum): causes flaccid paralysis (paralysis due to complete muscle relaxation) by inhibiting release of ACh- is injected in botox

Question 9

What are the 2 types of NT receptors?

Answer 9

Ion channel linked receptor

G-protein coupled receptor

Question 10

How does an ion channel linked receptor work?

Answer 10

Mediates fast responses

Mediates all fast excitatory and inhibitory transmission

Glu binds to receptor, stimulates receptor and allows it to open- influx of Na+ and generation of AP

Excitatory ion linked channel open Na+ channels in same was as Glu opens channel

Inhibitory ion linked channel usually opens Cl- channels

Question 11

How does a G- protein coupled receptor work?

Answer 11

Mediates slow responses

Effectors may be enzymes (adenyl cyclase, phospholipase C, cGMP-PDE) or channels (Ca2+ for example)

G protein coupled receptor has 7 transmembrane (7-TM) segments

When stimulated by agonist (NT) it activates G protein in membrane

G protein couples to effector which changes production of cAMP

Question 12

What are examples of ion channel linked receptors?

Answer 12

CNS: glutamate, GABA

Neuromuscular junction: ACh at nicotinic receptor

Question 13

What are examples of G- protein coupled receptors?

Answer 13

CNS and PNS: ACh at muscarinic receptors, dopamine, noradrenalin, seretonin, neuropeptidases (e.g. enkaphalin)

Question 14

What is an excitatory postsynaptic petential (EPSP)?

Answer 14

Influx of an ion causes an increase in membrane potential

Question 15

What is an inhibitory postsynaptic potential (IPSP)?

Answer 15

Influx of ions into postsynaptic cell causes decrease in membrane potential

Question 16

What is a glutamate receptor?

Answer 16

Ion lcannel linked receptor- excitatory

2 types:

AMPA receptor

NMDA receptor

Question 17

What is an AMPA receptor?

Answer 17

Mediates majority of fast excitatory synapses

Have rapid onset, offset and desensitisation

Question 18

What is an NMDA receptor?

Answer 18

Mediates slow component of excitatory transmission

Serve as coincidence detectors which underlie learning mechanisms

Question 19

What process occurs at a Glu synapse?

Answer 19

Glutamate synthesised from glucose via TCA cycle and transamination and loaded into vesicles

Glu released and binds to postsynaptic recemptors (NMDA and AMPA)

Gu is inactivated and reuptaken in presynaptic terminal or by glial cells through excitatory amino acid transporters

In glial cell, glu is enzymatically modified by glutamate synthetase to glutamine

Question 20

What causes seizures?

Answer 20

A balance needs to be maintained between glutamate and GABA

If theres too much synaptic glutamate we see increase spiking on ECG

This abnormal cell firing can lead to seizures

Question 21

What is epilepsy?

Answer 21

Characterised by recurrent seizure activity due to abnormal neural excitability (overactivity and uncontrolled glutamate activity)

Drugs which target GABA synapse are used

Question 22

What is a GABA receptor?

Answer 22

inhibitory receptor

Opens chloride channel

Influx of Cl- leads to hyperpolorisation

Question 23

What happens at an inhibitory GABA synapse?

Answer 23

GABA synthesised by decarboxylation of glutamate by glutamic acid decarboxylase (GAD)

GABA loaded into vesicles and releasedinto cleft

GABA binds to GABA A receptors and opens a chloride channel- Cl- influx and hyperpolorisation in post synaptic cell

GABA is inactivated by reuptake by GABA transporter (GATs)

OR GABA is taken up by glial cellsand enzymatically modified by GABA-transaminase to succinic semialdehyde

Question 24

How is GABA receptor structured?

Answer 24

Pentameric organisation of GABA receptor provides pharmacologically important binding domains

Question 25

What drugs facilitate GABA transaminases?

Answer 25

Antiepileptic

Anxiolytic

Sedative

Muscle relaxnant