Chem and physiol of the synapse Flashcards
NT TYPES AND ACTIONS
i) name the four main types of NT and give an example of each
ii) do NTs bind only one or multiple receptors?
i) 1) amino acids (Glu, GABA, Gly)
2) Monoamines (DA and 5HT)
3) Ach
4) Neuropeptides (endorphins)
ii) many
POST SYNAPTIC RECEPTORS
i) what speed of post synaptic potentials do ligand gated ion channels cause?
ii) what speed of post synaptic potential do GPCRs cause?
iii) what class receptor does Ach bind to in skeletal muscle? which ion moves across the membrane? what does this cause?
iv) what class of receptor does Ach bind on the heart? which ion channel opens? what does this cause?
i) very fast
ii) slow
iii) Ach binds nicotinic receptors in skeletal muscle which causes Na+ channel to open and depolarisation
iv) Ach binds muscarinic in the heart which is a GPCR - activation opens a K+ channel and causes slow hyper polarisation
IONOTROPIC RECEPTORS
i) what are they gated by? how fast is their transmission?
ii) what happens when a NT binds these channels? (3) how many subunits may the channel be made from? (2)
iii) which ions do Glutamate receptors flux? what type of post syn potential does this cause in the post synaptic neuron?
iv) which ions do GABA receptors flux? what type of post syn potential does this cause in the post synaptic neuron? which NT could counteract this?
v) name three other ligands that activate inotropic receptors
vi) give an example of a well studied inotropic receptor
i) gated by ligands (NTs)
ii) NT binds > channel changes confirmation > opens and ions flux through central pore
iii) Glu receptors flux Na+ which causes an excitatory post synaptic potential (EPSP) which depol the post syn neuron
iv) GABA receptors flux Cl- which causes an inhibitory post syn potential (IPSP) which hyperpolarises the post syn neuron - can be overcome if there is enough glutamate stimulation to counteract it
v) ATP, Ach and serotonin
vi) nicotinic receptor at the NMJ that is activated by Ach
DEFINITIONS
i) what is the receptor pharmacology?
ii) what are the kinetics of a receptor?
iii) what is the selectivity of a receptor?
iv) what is the conductance of a receptor?
i) what transmitter binds to the receptor and how drugs interact with them
ii) rate of transmitter binding and channel gating that determines the duration of effects
iii) which ions are fluxed (pass through)
iv) the rate of flux that helps determine the magnitude of effect
what voltage does the membrane rest at?
-65mv
GLUTAMATE RECEPTORS
i) what are the three main types of ionotropic glutamate receptors
ii) what is the agonist and antagonist of each?
iii) which receptor needs a co-factor to open?
i) 1) NMDA 2) AMPA 3) Kainate
ii) NMDA - agonist is NMDA and antagonist is APV
AMPA - agonist is AMPA and antagonist is CNQX
Kainate - agonist is kainic acid and antagonist is CNQX
SELECTIVITY AND CONDUCTANCE OF GLU RECEPTORS
i) which two receptors are non NMDA receptors? how quickly do they open?
ii) which two ions are non NMDA Rs permeable to and which phase of the EPSP are they responsible for?
iii) which receptor has a slow opening channel? what ion is it permeable to in addition to Na and K?
iv) which extracellular co-factor do NMDA receptors require to open the channel? what is this receptor also gated by?
v) which ion plugs a pore in the NMDA receptor at resting membrane potential? what happens when the membrane is depolarised? what is this known as?
vi) what phase of the EPSP are NMDA receptors responsible for? what state does the membrane already need to be in for these receptor to be activated?
i) AMPA and kainate - open fast
ii) AMPA and kainite are permeable to Na and K and are responsible for the early fast phase of the EPSP
iii) NMDA is a slow opening channel and is also permeable to Ca2+
iv) NMDA receptors require glycine as an extra cell co-factor to open - also gated by membrane volateg
v) Mg2+ plugs a pore in the receptor at rest - on depolarisation the Mg is ejected from the pore by electrostatic repulsion and other cations can flow through - known as activity dependent synaptic modification
vi) NMDA responsible for late phase EPSP
- membrane already needs to be depolarised
NMDA RECEPTORS
i) which two conditions need to be met for the receptor to open?
ii) influx of which two ions allows activation of enzymes that cause widespread changes in the post syn cell? what is this known as?
iii) what process may the action of these receptors be involved in the molecular mechanism for?
i) 1) an already depolarised membrane 2) Extracellular glycine as a co-factor
ii) influx of Na and Ca
iii) long term memory formation
DYSREGULATION OF NMDA RECEPTORS
i) what condition can be caused by dysregulation of NMDA channels?
ii) name two molecules that can inhibit the receptor? where do these bind? what does this therefore cause?
iii) which class of drug can enhance current flow through NMDA channels?
iv) what is excessive Ca influx into the cell associated with? how does this happen? in what situation may this occur (3)
i) schizophrenia
ii) PCP and MK801 bind the open pore and dont allow flux of ions through (causes hallucinations)
iii) some antipsychotics can enhance current flow
iv) excessive calcium influx can be associated with glu excitotoxicity - activates calcium dependent enzymes that degrade proteins, lipids and nuc acids - can occur after cardiac arrest, stroke, oxygen deficiency and repeated seizures
OTHER IONOTROPIC RECEPTORS
i) where do GABA and Glycine act? are they excitatory or inhibitory?
ii) what effect does nicotine have at the NMJ? what effect does it have in the CNS (2)
iii) what action does serotonin have (2) iv) what action does ATP have?
i) GABA in brain and Gly in sp cord and brainstem = inhibitory
ii) nicotine is excitatory at the NMJ and is excite or modulatory in the CNS
iii) excite or modulatory iv) excite
METABOTROPHIC RECEPTORS
i) how do they transduce signals? what can this lead to?
ii) how many receptors have been described for every known transmitter?
iii) what receptor does noradrenaline bind and what G protein does it activate? what does this result in?
iv) what receptor does glutamate bind? which G protein and second messenger does it activate? what does this result in? (2)
v) what receptor does dopamine activate? hich G protein and second messenger does it activate? what does this result in?
i) transduce signals through activation of a G protein which can lead to channel o pening
ii) many
iii) noradrenaline binds beta adrenergic > activates Gs > adenylate cyclase > increased protein phosphorylation
iv) Glu binds mGluR > Gq > PLC > inc protein phos and activates calcium binding proteins
v) dopamine activates D2 receptors > Gi | Aden cyclase > decreases protein phos
G PROTEINS
i) what is the hetromer comprised of? what’s it bound to in the resting state?
ii) what happens on the binding of a ligand (2)
iii) which subunit has intrinsic GTP-GDP enzymatic activity?
iv) what do Gq, Gi and Gs stimulate/inhibit
v) which ion channel do beta gamma channels activate? what speed of transmission does this allow?
i) alpha, beta, gamma - bound to GDP in resting state
ii) ligand binds and GDP is switched for GTP and hetromer splits
iii) alpha subunit has intrinsic GTP-GDP activity
iv) Gq > PLC > DAG and IP3, Gs > aden cyclase > cAMP, Gi inhibits adenylyl cyclase
v) beta gamma activate K+ channels
SECOND MESSENGER CASCADES
i) which G protein is activated when ligand binds the b site or the A2 site
ii) what does Gq activate?
iii) what does G protein signalling allow to happen do a signal? what can a weak signal end up as?
i) b site = Gs > cAMP . PKA, A2 site > Gi
ii) Gq activates PLC > DAG and Ip3 (DAG > PKC and IP3 to calcium)
iii) G protein signalling allows signal amplification - a weak signal can end up as an amplified
MODULATION BY RECEPTOR ACTIVATION
i) what can presyn receptors modulate?
ii) what do auto receptors do? give an example of this
iii) what do heteroreceptors do? give an example of how noradrenaline does this
iv) what can post synaptic receptors modulate? (2)
i) change amount of transmitter released
ii) auto receptors regulate their own NT by modulating synth, storage, release, reuptake eg phos of tyrosine hydroxylases
iii) heteroreceptors reg synth or release of NTs other than their own eg noradrenaline can influence release of Ach by modulating alpha adrenergic receptors
iv) post synaptic receptors can change firing pattern (inc or decrease firing rate) or have long term synaptic changes
TYPES OF RECEPTORS
i) which three glutamate receptors are inotropic?
ii) how many groups of metabotrophic glutamate receptors are there?
iii) name four other metabotrophic receptors
iv) name two ligands that can activate RTKs? what happens when these receptors are activated?
v) name a molecule that can permeate the membrane and act as a signal
i) NMDA, AMPA, kainate
ii) three groups
iii) metabotrophic = GABAb, muscarinic Ach (heart), dopamine, NE/adren receptors, 5HT, neuropeptide receptors
iv) NGF and BDNF > cause autophosphorylation
v) NO can cross cell mem and signal
