Flashcards in PA20023 Deck (160)
What receptors are found at excitatory synapses?
Transmitter interacts with receptors largely permeable to K+ and Na+
Eg acetylcholine binds to nicotinic ionotropic receptors at excitatory synapses creating an EPSP
What receptors are at inhibitory synapses?
neurotransmitter can Hyperpolarise the cell, and therefore inhibit from receiving further action potentials.
Hyper-polarisation is through chloride ions
Which is faster at generating an action potential, spatial summation or temporal summation?
When cells are close together, their action potentials can add up to reach threshold; many cells firing at Same time and their action potentials add up.
Whereas temporal is one cell firing in succession to try and generate an AP
Where are purkinje, pyramidal and the motor neurone found?
Purkinje neurones found in cerebellum
Pyramidal neurones found in cortex
Motor neurone is the big neurone in the spinal cord
Are endorphins (endogenous opioids) amino acids, purines, amines or peptide neurotransmitters? what about adenosine?
Endorphins are Peptides
Adenosine is a purine
GABA A and B, which one binds to ionotropic receptors?
GABA a binds to ionotropic
GABA b binds to GPCRs
What are EAATs?
Excitatory Amino acid transporters
They facilitate glutamate reuptake at synapses
Present in glial cell membranes and presynaptic cell membrane to allow glutamate reuptake, stored as glutamine in glial cells
What is monosodium glutamate?
A flavouring In food
It can actually kill some brain cells
Glutamate is involved with exctitoxicity
How is glutamate stored in order to regulate its levels In the CNS?
Stored as glutamine in the Glial cells that sit in between neurones, it is synthesised from glutamine by phosphate activated glutaminase enzyme within a presynaptic cell when it's needed
How does glutamate bind to so many receptors?
It is flexible, it can rotate around its alpha beta and beta gamma bond.
At least 9 different rotamers are possible
The __ elements of ionotropic receptors form the pore. How?
They are part of each of the 4 subunits that form these receptors, they're subunit 2. They associate and bring the subunits all together in an orientation that forms a pore/ channel.
what subunit is present in the AMPA receptor will make it impermeable to calcium? When is it permeable to calcium?
GluA2 subunit present= not permeable to Ca
Homomeric GluA1 receptor= is permeable to Ca
Remember it's also permeable to Na+ in and K+ out
Is NMDA receptor permeable to calcium? How does is compare to the AMPA receptor?
Vastly permeable to calcium, doesn't depend on subunit composition like AMPA.
It lets more calcium in than AMPA even when it is permeable
What is a co-agonist of the NMDA recpetor?
NMDA receptor can only be activated when glycine is present
You need another agonist too; NMDA, glutamate, aspartate
The different properties of the AMPA and NMDA receptors give the fast and slow time course of an EPSP. Which does which?
AMPA: fast on fast off (fast depolarisation)
NMDA: slow on slow off (slow depolarisation)
NMDA receptors are dual gated, what does this mean?
They're both voltage gated an ligand gated.
The channel of NMDA is blocked by Mg2+, which only moves when depolarisation occurs.
NMDA receptor needs both glutamate and depolarisation to work
What effect do mGluRs have on calcium, and on glutamate release?
mGluRs are metabotropic receptors
In presynaptic cells they lead to calcium channel closure, which leads to less glutamate release.
In postsynaptic cells they lead to K+ channel closure.
This leads to reduced K+ efflux out of the cell and slow depolarisation
Also glutamate binding to mGluRs in postsynaptic cell leads to an increased level of intracellular calcium.
What two receptors are involved with glutamate release control?
Presynaptic NMDA (ionotropic) and presynaptic mGluR's.
Presynaptic NMDA r increases glutamate release by increasing calcium influx.
Presynaptic mGLuRs decrease glutamate release by decreasing Calcium influx
GABA is synthesised from _____.
The enzyme that catalyses this is _____.
GABA is further converted into _____, by the enzyme ____.
Drugs acting on these enzymes to increase levels of GABA can be used as _______.
Synthesised from glutamate
By the enzyme glutamic acid decarboxylase
Further converted to succinate
By the enzyme GABA transaminase
Drugs acting on these enzymes can be used as anticonvulsants in epileptics, as GABA is inhibitory.
GABA a receptor (ligand gated ion channel, ionotropic) agonists?
GABA B receptor (GPCR) agonists?
GabaA: agonists are GABA and Muscimol
GABA B: agonists are GABA and baclofen
What is baclofen used to treat?
It binds to GABA B receptors
Inhibits motor neurone activation via the spinal cord
Major side effect: sedation, as baclofen crosses the BBB, inhibits brain activity making you sleepy
Where do benzodiazepines act?
They can be agonist or inverse agonists of the modulator site of GABA A receptors.
They're allosteric modulators, and they bind at the interface between the alpha and gamma subunits of the GABA A receptor.
GABA binds between the alpha and beta subunits
What are benzodiazepines actions?
Bind to GABA A so have inhibitory effects
Anxiety relieving, anticonvulsant and Hypnotic.
Note: they can be agonists, antagonist and inverse agonists
What are etomidate and propofol? Where do they act?
Act at GABA A receptors
Cross BBB and inhibit brain neuronal activity, making you sleepy
What effects do barbiturates and phenobarbital have?
Sedative/ anti convulsive
Calm down muscle activity
They can increase inhibition of nervous activity in the brain to the point of death
Remember barbiturates act on GABA A receptors, they're channel modulators and stimulate the receptor to further inhibit motor pathways
What do Neurosteroids bind to?
Bind to GABA receptors
Metabolites of progesterone & deoxycortisone
Where does ethanol ( Alcohol ) bind in the CNS?
Binds to GABA A receptors
Alcohol has a depressant effect on the CNS
It increases GABAnergic inhibition
Diazepam and lorazepam are Benzodiazepines. How do they make you feel?
They are calming
They are anxiolytics (anti anxiety)
They are NOT sedative
Nitrazepam, flurazepam and temazepam are all Benzodiazepines. How do they make you feel?
So they makes you fall asleep
Used to treat insomnia
Remember benzodiazepines act on GABA A receptors, they're channel modulators and stimulate the receptor to further inhibit motor pathways