Lecture 7 NS - Neurotransmitters

Question 1

What is necessary for neurotransmission to occur?

Answer 1

Release of neurotransmitters and their interaction with postsynaptic receptors

Question 2

What are the 3 stages of synaptic transmission?

Answer 2

Transmitter released from 1st cell, synaptic activation of second cell and signal integration/conduction by 2nd cell

Question 3

What are the main points about synaptic transmission?

Answer 3

Rapid timescale, diversity, adaptability, plasticity, learning and memory

Question 4

What is the structure of the cell body?

Answer 4

Question 5

How large are synapses?

Answer 5

20-100 nm

Question 6

Where are NT contained?

Answer 6

Synaptic vesicles

Question 7

Why are mitochondria present?

Answer 7

Synaptic transmission is a very high energy process

Question 8

What is the postsynaptic density?

Answer 8

Electron dense material underneath synapse with signalling proteins which mediate a number of pathways which happen in response to cell activation

Question 9

What are the 3 stages of synaptic transmission?

Answer 9

Biosynthesis, packaging and release of NT, receptor action and inactivation of NT

Question 10

What are neurotransmitters?

Answer 10

Provide enormous diversity in variety of transmitter and their receptors -> may mediate rapid or slower effect

Question 11

What are the most important NT?

Answer 11

Amino acids (glutamate (stimulates), GABA (inhibit), glycine), amines (NA, DA) and neuropeptides (opoid - endorphins)

Question 12

How do NT vary in abundance?

Answer 12

From mM to nM CNS tissue concentrations

Question 13

How do neurons produce diverse functional responses?

Answer 13

Neurons receive multiple transmitter influences which are integrated

Question 14

How is a CNS synapse activated?

Answer 14

Action potential arrives at nerve terminal which depolarises it, causing entry of Na and outflow of K -> Ca channels open and enter into cell which triggers NT release into the synapse which activates its receptors, to open Na channel, continuing the AP -> NT needs to be regulated which is controlled by desensitisation of receptors and removal of NT from synapse via transporters which rapidly remove NT from synapse -> NT is accumulated into vesicle ready to go, with Na pump pumping Na out to return to membrane potential

Question 15

How is ACh removes from the synapse?

Answer 15

ACh esterase breaks it down, present on postsynaptic membrane

Question 16

What are the essential components of synaptic transmission?

Answer 16

Restricted to specialised structures, fast, Ca is essential for NT release and synaptic vesicles provide source of NT

Question 17

How can rapid release of NT occur at the synapse?

Answer 17

Synaptic vesicles are filled with NT and docked in the synaptic zone ‘primed’ -> interaction between synaptic vesicle and synaptic membrane proteins allow rapid response -> Ca entry activated Ca sensor in protein complex

Question 18

What are some neurotoxins that target vesicular proteins?

Answer 18

Tetanus (paralysis) and botulinum toxin (Flacid paralysis)

Question 19

What is necessary for transmitter release?

Answer 19

Transmitter containing vesicles to be docked on presynaptic membrane; protein complex formation between vesicle, membrane and cytoplasmic proteins to enable vesicle docking and rapid response to Ca entry; ATP and vesicle recycling

Question 20

What is NT action defined by?

Answer 20

Receptor kinetics

Question 21

What are the 2 types of NT receptor?

Answer 21

Ion channel receptor and G-protein coupled receptor

Question 22

What is the difference between ion channel receptor and G-protein coupled receptor?

Answer 22

ICR: fast (msecs), mediates all fast excitatory and inhibitory transmission -> just a channel. GCPR: slow (s/min), effectors may be enzymes (PLC) or channels (K or Ca) -> made up of receptor, g-protein and effector

Question 23

What are some examples of ion channel receptor?

Answer 23

CNS: glutamate, Gamma amino butyric acid (GABA). NMJ: ACh at nicotinic receptors

Question 24

What are some examples of G-protein coupled receptors?

Answer 24

CNS/PNS: ACh at muscarinic receptors, DA, NA, 5-hydroxytryptamine and neuropeptides

Question 25

What are ion channel linked receptors?

Answer 25

Rapid activation, diversity and rapid information flow, multiple subunit combinations-distinct functional properties

Question 26

What are the 4 different ion-channel linked receptors?

Answer 26

Nicotinic cholinergic receptors, glutamate, GABA, glycine receptors -> GLUR (Na), GABAR (Cl), GlyR (Cl)

Question 27

What is the difference between inhibitory and excitatory NT receptor?

Answer 27

GluR -> Na entry, so depolarisation enters, so EPSP, GABAR -> Cl entry so hyperpolarisation so threshold for response has been changed

Question 28

What are the 2 types of glutamate receptors?

Answer 28

AMPA receptor and NMDA receptor

Question 29

What does the AMPA receptor do?

Answer 29

Na+. Majority of FAST excitatory synapses w/rapid onset, offset and desensitisation

Question 30

What does NMDA receptor do?

Answer 30

Na+ and Ca2+. Slow component of excitatory transmission, serving as coincidence detectors which underlie learning mechanisms

Question 31

What does the Ca that enters NMDA do?

Answer 31

Modifies the AMPA receptor potentiating AMPA receptor response and activates protein synthesis which modifies synapse formation

Question 32

What occurs in an excitatory CNS synapse mediated by glutamate?

Answer 32

Glutamate made from glucose in TCA -> released in synapse and reacts with GLUR, letting Na or Na/Ca in. To remove Glut from the synapse, excitatory a.a. transporters present on nerve and glial cells take up the glut -> in glial cell glut is broken down [glutamine synthetase] into glutamine, which is inactive

Question 33

What is epilepsy?

Answer 33

Common neurological condition, characterised by recurrent seizures due to abnormal neuronal excitability (leading to increased glutamate release) -> despite advances in modulating seizure generation and propagation, the disease is disabling -> 30% refractory to treatment

Question 34

How do CNS inhibitory synapses mediated by GABA work?

Answer 34

GABA is synthesised from glutamate by GAD, then released and acts upon GABAR which has an inhibitory effect due to Cl entering the post-synaptic cell -> inactivated by GABA trans-aminase in glial and presynaptic cell into succinate semialdehyde

Question 35

Why is succinate semialdehyde helpful?

Answer 35

It can enter the TCA cycle via a GABA shunt

Question 36

How is the GABA receptor targeted by pharmacological components to dampen down excitatory activity?

Answer 36

Question 37

What do benzodiazepines do?

Answer 37

Increase fequency of channel opening

Question 38

What do barbiturates do?

Answer 38

Increase duration of channel being open

Question 39

What is the focus of epilepsy treatment?

Answer 39

Damping down excitatory activity by facilitating innhibitory transmission

Question 40

Where do benzodiazepines and phenobarbital act upon in the GABA synapse?

Answer 40

On GABA[A] receptor on 2 different sites, increasing inhibitory activity of GABA

Question 41

Where does tiagabine act upon in the GABA synapse?

Answer 41

It is a competitive inhibitor of the GABA transporter, so more GABA is available for receptor binding on the surfaces of post-synaptic cells

Question 42

Where does vigabatrin act upon in the GABA synapse?

Answer 42

It acts upon GABA-T (enzyme) to prevent the break down of GAB, leaving more GABA available for exocytosis into synapse