Week 11 - Neurotransmission

Question 1

How is an action potential (AP) generated

AP is an electrical signal

Answer 1

AP occurs when a neuron sends info down axon
- neurones can alter their membrane potential
- axon is surrounded by myelin sheath (insulates axon = speeds up conduction of signal)

PROCESS:
1. Have membrane resting potential = -70mV
2. Small depolarisation causes Na+ to enter cell down an electricochemical gradient
- influx causes more Na+ channels to open
3. Membrane potential reaches threshold (+30mV) and Na+ channels close and K+ channels open
4. K+ leaves cell down electrochemical gradient = repolarisation
5. K+ channels take time to close = hyperpolarisation occurs <-70mV (due to too much loss of K+)
6. Membrane potential is then brough back to resting potential of -70mV

NOTE:
- have more Na+ outside of cell
- Na+ = excitatory
- have more K+ inside of cell
- K+ / Cl- = inhibitory

Depolarisation = +ive ions entering cell
Hyperpolarisation = -ive ions entering cell OR +ive leaving

Question 2

Explain the neurotransmission process

Inc. arrival of AP, neurotransmitters, synapse

Answer 2

Neurotransmitters are stored in synaptic vesicles (in pre-synaptic neurone)

1. AP travels down pre-synaptic neurone to axon terminals
2. AP causes voltage gated Ca2+ channels to open = influx of Ca2+
3. Ca2+ triggers exocytosis of synaptic vesicles = neurotransmitter released
   - conversion from electrical signal (AP) to chemical signal (n.transmitter) that can cross synapse
4. Neurotransmitter diffuses across synapse + binds to receptors on post-synaptic neurone membrane
   - receptors determine if signal is excitatory or inhibitory

How do you prevent over-excitation by neurotransmitters
1. Inactivation
- enzymes in synaptic cleft break down n.transmitter
- the precursors are taken up
2. Reuptake
- channlels on pre-synaptic neurone, transmitters are taken up through it + recycled and stored

Question 3

What is an agonist and antagonist

Answer 3

Agonist - binds to receptor, causing activation of the receptor

Antagonist - binds to receptor (preventing agonist from binding) = no receptor activation

Partial agonist - binds to receptor causing partial activation (weak activation)

Question 4

What are the 3 receptor types

Answer 4

1. Ionotropic Receptor
   A ligand-gated ion channel
   
   • when ligand binds = conformational change = channel opens = ions can flow into cell
   • very RAPID response
   • fast neurotransmission process
2. Metabotropic Receptors
   A G-protein coupled receptor
   
   • when agonist binds = conformational changes
   • slower response
   • slower neurotransmission processes
   • e.g. Dopamine receptors

Question 5

How is dopamine synthesised

Answer 5

Precursor for dopamine is L-Tyrosine

1. L-Tyrosine is converted into L-Dopa by tyrosine hydroxylase
   - tyrosine hydroxylase is rate-determining step as enzyme is saturable
2. L-Dopa is converted into Dopamine by dopa decarboxylase (DDC)
   - DDC is not saturable = can have as much L-dopa and all will be converteed

Dopamine Receptors:
- D1 = excitatory
- D2 = inhibitory

Question 6

How is dopamine inactiavted / re-uptaken

Answer 6

1. Inactivation
   
   • metabolism by enzyme
   • enzyme inc. COMT, MAO
2. Reuptake
   
   • via DAT (dopamine transporter) on pre-synaptic terminal

Question 7

What is parkinson’s disease

Answer 7

Is when you have a loss of dopamine neurones (= less dopamine being released)
- approx. 60-70% loss

TREATMENT:
1. L-dopa (NOT L-Tyrosine as the enzyme is saturable)
- DDC (enzyme) is not saturable and will convert all L-dopa into dopamine
2. Dopamine (D1) agonist