L 9 Synapses And Neurotransmitters - Pt 2 Flashcards
What are the criteria for neurotransmitters?
- Should be present in presynaptic terminal.
- Should be released in response to stimulation.
- Should act on the postsynaptic neuron.
Blocking neurotransmitter should prevent synaptic transmission
What does immunostaining do?
It helps visualise specific proteins within cells or tissues.
- Fluorescent dyes
- Enzymes that produce a colored product
What does in situ hybridisation do?
Helps to determine whether the cell expresses enzymes to synthesis it, or transporter proteins to store neurotransmitters.
Explain the Loewi’s 1921 experiment
Collect fluid around neurons after stimulating them
How do we know if the neurotransmitter affects the postsynaptic cell?
Test if the molecule mimics the effect of stimulating the presynaptic cell
How do we block the neurotransmitter?
Apply drugs; delete genes encoding enzymes/ transporters/ receptors
What are the 3 types of neurotransmitters?
Amino acids
Amines
Peptides
What are co- transmitters?
Often peptide-releasing neurons also release a small molecule transmitter, called a ‘co-transmitter’
How big are the 3 types of neurotransmitters?
Amino acid and amines are 100 - 200 Da
Peptides are large molecules with 1000 - 3000 Da.
Where are the 3 types of neurotransmitters stored in?
Aminoacid and amines are stored in synaptic vesicles.
Peptides are stored in secretory granules.
What can the 3 types of neurotransmitters bind to?
Amino acid and amines can bind to ligand-gated ion channels or g-ptotein coupled receptors.
Peptides can bind only to G-protein coupled receptors.
Give me 2 types of neurotransmitters receptors
- Ligand gated ion channels.
- G Protein coupled receptors.
What happens when a neurotransmitters bind binds to a ligand-gated ion channel?
It directly depolarise or hyperpolarise the postsynaptic cell.
Can a transmitter activate multiple receptors?
Each transmitter can activate multiple different receptors (divergence)
Explain what divergence is
Different transmitters or receptors can activate the same downstream effector (amplifies the effect)
What is the most common excitatory transmitter in CNS?
Glutamate
What are the 3 ionotropic glutamate receptor subtypes based upon?
They are based on the drugs which acts as selective agonists.
What are the 3 glutamate receptors called?
- AMPA receptors
- NMDA receptors
- Kainate receptor
How is the action of glutamate terminated?
Terminated by selective uptake into presynaptic terminals and glia.
Do AMPA receptors mediate fast or slow excitatory transmission?
They mediate fast excitatory transmission.
What are the effects of glutamate binding to AMPA receptors?
Triggers Na+ and K+ currents resulting in an EPSP.
Which 2 ionotropic glutamate receptors often co- exist with each other
NMDA receptors often co-exist with AMPA receptors
Which glutamate receptor have a voltage- dependent Mg2+ block?
NMDA receptors
When do NMDA receptors open?
When neuron is already depolarised.
NMDA receptors let Ca2+ in… what does this lead to?
Leads to downstream signalling.
What is mGluRs?
Metabotropic glutamate receptors, they allow glutamate to sometimes be inhibitory.
What are metabotropic receptors?
They are G-protein coupled receptors.
Give me 2 example receptors of mGluRs
mGluR1, mGluR2
Describe the mechanism of ionotropic and metabotropic receptors
Ionotropic receptors - Opens ion channels.
Metabotropic receptors - Activates G-protein, trigger downstream signalling cascade.
Which receptor produces a faster response, ionotropic or metabotropic?
Ionotropic responds in msecs.
Metabotropic - seconds to minutes.
Do mGluRs allow inhibitory response to glutamate?
Yes sometimes, eg: retina.
What is the most common inhibitory transmitter in the CNS?
GABA
How is GABA an inhibitory transmitter? What does it do?
GABA produces IPSPs (inhibitory postsynaptic potentials) via GABA-gated chloride channels (GABAA receptors), if the membrane potential is above chloride’s Nernst potential
What happens if GABA inhibits too much/too little neurotransmitters?
The right amount of inhibition via GABA is critical:
- Too right = coma or loss of consciousness
- Too little = seizures
What are the other 4 chemicals that can bind to GABA receptors?
- Ethanol
- Benzodiazepine
- Barbiturate
- Neurosteroids
Can other chemicals bind to GABA receptor and inflict any effects by itself?
These chemicals have no effects without GABA binding (allosteric drug)
What are barbiturates?
They are sedatives and anti convulsants.
What are benzodiazepines used for?
They are used to treat anxiety. eg. diazepam.
What are the effects of GABA binding to GPCRs?
GABA binding to GPCRs triggers a cascade of intracellular events:
- Open K+ channels
- Close Ca2+ channels
- Trigger other second messengers like cAMP
What is GPCR?
G protein-coupled receptors
How do GPCR receptors work?
- When a signaling molecule (like a hormone or neurotransmitter) binds to a GPCR, it causes a conformational change in the receptor
- This change activates a G protein, which is loctaed on the inside of the cell membrane
- This activated G protein then triggers a cascade of intracellular signaling events, leading to a cellular response
What are mGluRs and GABA receptors like?
They’re like GPCRs
What is the function of GABA_B receptors located on the neuron that releases GABA?
Presynaptic or auto inhibitory
What does glycine do?
Glycine inhibits neurons through glycine-gated chloride channel.
What is dendritic integration?
A neuron’s dendrites combine and process the multiple synaptic inputs they receive
What is temporal summation?
Inputs arriving at the same location in quick succession are combined
What is spatial summation?
Inputs arriving at different locations on the dendrites are combined.
Does it matter how excitatory and inhibitory synapses are arranged spatially?
Yes it matters
Can an inhibitory synapse block the propagation of an EPSP toward the soma?
An inhibitory synapse can block the propagation of an EPSP toward the soma
What is Vm?
Membrane potential
Do GABA receptors always produce an IPSP ?
No they dont always produce an IPSP.
What is shunting inhibition?
Shuntin inhibition is when GABAA receptors don’t always produce an IPSP, e.g. if Vm is near chloride’s Nernst potential
What are the effects of chloride conductance?
Opening chloride conductance decreases the membrane resistance -> current leaks out the membrane
Where does inhibition often occur?
It often occurs presynaptically.
Explain the process of presynaptic inhibition
1) Action potential arrives
2) Less calcium enters due to the GABA release which inactivated calcium channels
3) Less Ca2+ = less neurotransmitter released
4) Reduced effect on postsynaptic membrane
If AMPA receptors are permeable to both Na+ and K+, why does activating them cause depolarisation?
Glutamate binding to AMPA receptors triggers Na+ and K+ currents resulting in an EPSP
What are ESPSs?
Excitatory Postsynaptic potentials
What would happen if GABA opens a GABAA receptor and the membrane potential is below chloride’s Nernst potential? Would you get net inflow or outflow of chloride ions?
Produces IPSPs (inhibitory postsynaptic potentials) via GABA-gated chloride channels (GABAA receptors), if the membrane potential is above chloride’s Nernst potential
