Neuroscience & Basics Flashcards
Explain the resting membrane potential of a neurone
In which direction does K+ and Na+ flow from the neurone?
How is the neurone described at this potential?
What are the 6 steps following this state of the neurone to fire an action potential?
When 2 K+ moves outside freely for every 3 Na+ moving inwards by the Na+-K+ pump, producing an overall potential of -70mV
K+ out, Na+ in
Polarised
- Local potentials depolarises the membrane to above the -40mV threshold
- more Na+ voltage gated channels open and K+ voltage gated channels close - allowing high influx of Na+ into the cell
- Charge of the membrane +40mV = action potential
- Na+ channels inactivated and K+ channels open allowing K+ to move out of the cell to re-polarise the neurone
- Hyperpolarisation at -90mV
- K+ channels close, allowing cell to depolarise back to -70mV at resting potential
What is the difference in the action potential transfer between neurones in a myelinated and unmyelinated neurone?
Myelinated neurones - have to propagate along and relies on Na+ channels opening in the nodal spaces (between myelin)
Unmyelinated - Na+ channels opened across the entire length of the axon
What are the 4 steps for synaptic transmission once the action potential reaches the synaptic terminal?
What are the 6 ways that an agonist drug can act at the synapses?
What are the 5 ways an antagonist drug can act at the synapses?
- Ca2+ channels open as a result of depolarisation
- Vesicles in the synaptic terminal fuse with the pre-synaptic membrane
- Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the post-synaptic membrane
- Neurotransmitter is then eliminated from the post-synapse by re-uptake into the pre-synapse or degradation
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- Precursor - synthesise NTs
- Enhance release NTs into synaptic cleft
- Mimic NTs and bind to post-synaptic neurone receptors
- Block degradation of transmitters
- Block activity of autoreceptors (regulate firing patterns of neurones)
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- Reduce synthesis NTs
- Make vesicles leaky - don’t transport/fuse to membrane
- Inhibit exocytosis/release NTs
- Block NT binding on post-synaptic membrane
- Hyperpolarise -90mV at terminal so no AP
How to ionotropic receptors mediate a response?
Are they inhibitory or excitatory?
What is their structure?
What kind of regulation occurs when ligand binds?
Ligand binds and mediates opening/closing of an ion channel
Depends on ion species
4-5 transmembrane subunit forming the ion channel complex with a receptor moiety for neurotransmitter binding
Allosteric - such that allows for ion pore to be opened/closed whether ligand has bound
What is the structure of a metabotropic receptor?
What is the response when the receptor is G i/o coupled?
G s coupled?
G q coupled?
7-transmembrane domain coupled with a G-protein
a-i inhibits adenylyl cyclase (ATP->cAMP->PKA)
a-s activates adenylyl cyclase
a-q activates PLC-ß to convert PI(4,5)P2 -> DAG (PKC) and IP3 (Ca2+)
What are the 4 requirements for a neurotransmitter?
What are the 3 types of neurotransmitters?
What are the characteristics of each?
What is a NT system?
- Stored & synthesised in presynaptic neurones
- Released presynaptically on stimulation
- Molecule acts like a transmitter - mimicry
- Must be removed from synaptic cleft
Amino acids, small molecules & peptides
AA = small, fast acting & found throughout CNS
SM = middle sized, fast & modulatory actions & wide acting - produced in specific nuclei
P = large, slow & specialised & produced in specific neurones & released with other NTs
Collection proteins responsible for synthesis, function, response & termination of an action
What kind of response does glutamate form?
How is glutamate produced?
What happens after its production?
What happens after the vesicles fuse with the pre-synaptic membrane & are released into the synaptic cleft? (after binding to receptors on post-synaptic membrane)
How is it recycled/broken down?
What are the 6 different types of glutamate-responding receptors & what is their function?
Excitatory - brain function
General metabolism in pre-synaptic neurone from aspartate & glutamine
Packaged into vesicles
Taken up by EAAC transporters in pre-synaptic neurone and GLAST/GLT-1 in glia cells
Glutamate converted into glutamine in glia cells and then glutamine is released & taken up by neurones
- AMPA - ion channel excitation
- Kainate - ion channel excitation
- NMDA - ion channel excitation with coincidence detection & memory
- mGluR group 1 - Gq coupling - excitatory modulation
- mGluR group 2 - Gi/o - inhibitory modulation
- mGluR group 3 - Gi/o - inhibitory modulation
What kind of receptor is NMDA & what NT does it respond to?
What function is it associated with?
How is the receptor at resting potential?
How is the receptor activated?
What happens when the neurone depolarises/activated?
What happens when NMDA is overstimulated?
Post-synaptic ionotropic (ion/ligand-voltage gated) - glutamate AND voltage (but typically one or the other)
Visual systems/epilepsy, associative learning, pain transmission, memory & cell death
Mg2+ plugs the receptor preventing flow of ions in/out
Receptor strongly/repeatedly stimulated (ligand binding)
Mg2+ removed allowing K+ move out & Na+/Ca2+ move in
Epileptic activity & wind-up of the spiral cord enhancing pain level transmission
What kind of receptor is AMPA?
What ligand/NT binds to it?
How is the receptor activated?
What does an antagonist do generally when they bind to AMPA receptors?
What kind of response does Kainate receptor produce?
What kind of receptor is mGluR?
Post-synaptic ionotropic
Glutamate
Glutamate binds & opens Na+ channels allowing Na+ flow inside neurone (depolarisation)
Global blocking of excitation
When glutamate binds - fast excitatory response
Metabotropic - G-protein coupled
What kind of NT is GABA?
How is it synthesised?
How is it taken up after release?
What happens after?
What happens when an agonist drugs/GABA binds to a GABA-A receptor?
Typically then what are the agonist drugs?
What kind of response does GABA-A receptors produce?
What are the 5 different sites of the GABA-A receptor?
What kind of drugs are benzodiazepines?
Barbiturates?
What kind of drugs can bind to the steroid site?
Amino acid
From glutamate
GABA transporters in astrocytes (glia cells)
Metabolised by GABA-T in astrocytes & released for uptake by neurones
Opening of Cl- channel allowing Cl- flow into post-synaptic neurone for inhibitory hyperpolarisation blocking AP
Depressants/sedatives
Inhibitory response
- GABA site
- Benzodiazepine site
- Barbiturate site
- Steroid site
- Picrotoxin site
Agonists & antagonists/inverse agonists - sedatives, anti-epileptic agents
Sedatives (anaesthesia) - opens Cl- channel
Anaesthetics (agonist) or anxiogenics (antagonist)
What do GABA-B receptors do on activation?
How are GABA-A & B receptors different?
What do drugs targeting GABA-B receptors treat?
What does glycine do?
What kind of NT is glycine?
G-protein coupled to open K+ or close Ca2+ channels via beta-gamma subunits of Gi/o coupled protein
GABA-A = ionotropic & GABA-B = metabotropic
Spasticity
Inhibits GABA-B - used in spinal cord
Amino acid
What kind of NT is acetylcholine?
Where is it synthesised?
Where are cholinergic neurones?
What are the 7 functions associated with acetylcholine?
What does ACh deficit have links to?
What are the 5 steps of ACh synthesis & recycling?
What are the 2 categories of ACh receptors?
Small molecule
3 distinct locations in the brain
Axons spread throughout
- Learning
- Memory
- Motor function
- Autonomic nervous system
- Disease
- Sleep
- Arousal
Alzheimer’s
- Synthesised from acetyl-coA & choline in pre-synaptic neurone
- ACh is pumped into vesicles in pre-synaptic neurone by transporter
- ACh released on arrival of an action potential & binds to receptors on post-synaptic neurone
- Degraded into choline & acetic acid by AChE
- Choline pumped back into presynaptic terminal
- Nicotinic (ionotropic) receptor
- Muscarinic (metabotropic) receptors M1 & M2
What type of response is produced when ACh binds to its nicotinic receptor (nAChR)?
Where are they located?
What type of response does the M1-type receptor produce and why?
M2-type receptor?
Excitatory - allowing K+ out and Ca2+/Na+ in
Plasma membrane of neurones & neuromuscular junctions
Excitatory - coupled to G-q/11
- alpha-q activates PLC-ß and beta-gamma activate K+/Ca2+ channels & inhibit TRPM3 ion channels in sensory neurones
Inhibitory - coupled to G i/o so inhibits adenylyl cyclase but beta-gamma does same as above
What kind of NT is dopamine?
What are the functions of the 2 parts of the brain in which it is synthesised?
What are 8 functions of dopamine?
What are the 4 steps from dopamine synthesis to recycling?
What are the 2 categories of dopamine receptors & which types are included in them?
Small molecule
Substantia nigra in motor function & ventral tegmental area with reward, addiction & mesocortical/mesostriatal pathways
- Pain
- Mood
- Sex
- Motivation
- Motor control
- Liking/learning/wanting (mesocorticolimbic pathway)
- Hormone release regulation
- Thermoregulation
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- Synthesised from tyrosine by tyrosine-hydroxylase & dopa-decarboxylase
- Released from pre-synaptic neurone
- Taken up by dopamine transporter for re-uptake back into the pre-synaptic cytosol
- If the dopamine is not recycled & packaged back into vesicles, it is broken down by monoamine oxidase & catechol-O-methyltransferase
D1-like (D1+D5) stimulate adenylyl cyclase (G/s coupled)
D2-like (D2,3,4) inhibit adenylyl cyclase (Gi/o coupled)
Where is noradrenaline produced?
What are the 6 functions?
What are the 3 stages from synthesis to reuptake?
What do all 5 noradrenergic receptors have in common?
What receptors are Gs coupled? (adenylyl cyclase activating) And where are these located?
What receptors are Gi or Go & where are they located?
What receptors are Gq coupled?
Produced in neurones in locus coeruleus in the brain but expand over entire brain
- Learning/memory in central pathways
- Autonomic effects (sympathetic nervous system)
- Endocrine effects - adrenal glands
- Attention - central pathway
- Mood
- Regulates pain
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- Synthesised from dopamine by dopamine-ß-hydroxylase
- Released & taken up by noradrenaline transporter back into pre-synaptic neurone
- If it is not recycled, broken down by monoamine oxidase MAO & catechol-O-methyltransferase COMT
Metabotropic - G protein coupled
Beta-1 heart & kidney, Beta-2 peripheral nervous system & Beta-3 adipose tissue
Alpha-2 autoreceptor at presynaptic (non-) noradrenergic terminals & beta-2 PNS
Alpha-1 - postsynaptic through brain (like beta 1 & 2)
