Post synaptic events Flashcards
how does a neurotransmitter affect the post synaptic membrane?
opens channels
what is an EPSP?
excitatory post synaptic potential
- single EPSP may not be large enough to elicit an action potential
how does an inhibitory NT work?
- influx of chloride ions
- inhibitory EPSP
- Instead of depolarising it hyperpolarises the membrane
what are ligand gated ion channels?
- they are ion tropic
- receptor sensitive to NT
- when NT binds causes a conformational change to open the channel
- fast response
- can also be located on the presynaptic membrane (auto-receptor)
what are G protein coupled receptors?
- metabotropic
- 7 transmembrane spanning protein
- bound to a G protein
- G stands for GTPase
- signalling protein
- they are triemric
how do G proteins work?
G proteins bind to GTP and migrate/diffuse along the membrane and activate enzymes
- G protein subunits beta and gamma can interact with ion cahnnels
what sort of response are GPCRs?
- slow response
how was the structure of Acetylcholine receptor structure determined?
- used x-ray diffraction to look at arrays of the receptors in membranes
- electric ray, have an electric organ with lots of acetylcholine
what is the structure of acetylcholine receptor?
- ionotropic, nicotonic acetylchlline receptor
- metabotropic, muscarinic acetylcholine receptor
- 5 subunits: 2alpha, beta, gamma, delta –> pentameric
- each subunit has four TM domains
- M2 helix forms the pore
- large extracellular N terminal domain creates the ligand binding site
- each subunit forms a ring
what does acetylcholine receptor do?
- at the skeletal mucle neuromuscular junction it mediates muscle contraction
- CNS - key in the pre-frontal cortex whih regulates transmission
how do acetylcholine receptors work?
Ach molecules bind to the x-subunits causing the receptor to undergo a conformation change
- channel opens allowing cations to pass through due to large pore size
- regulates membrane potential of other synpases
what are two ionotropic receptors for glutamate?
- AMPA and Kainate
- NMDA
what is AMPA?
agonist: AMPA - drug
what is Kainate?
agonist: Kainic acid
what is AMPA and Kainate?
- fast EPSP via increase in conductance to monovalent cations
- permeable to Na+ and K+
- gated by glutamate binding
- produce rapid depolarisation that decays relatively rapidly
what is NMDA?
agonist: N-methyl-D-aspartate
what does NMDA do?
- Ca2+ dependent EPSP that is slower
- opens in the presence of glutamate and depolarisation of the post synaptic neuron
- needs a strong stimulus to overcome the Mg2+
- its gating Ca2+, will trigger signalling
what response do AMPA receptors mediate?
fast
what response do NMDA receptors mediate?
slow and long
what is glutamate?
- post synspase found on the dendritic shape
- sticks out from the dendrite, where the receptors are
- theres lots of proteins in the post synapse so very electron dense
- the whole of this complex is involved in learning and memory
- experience alters the spines on dendrites
what type of receptor is the GABA receptor?
iontropic
what happens if you have drugs promoting GABA binding?
they have an inhibitory effect
- benzodiazepines (increase binding tranquilizing activity)
- barbituates (treatment of elipsy)
- alcohol (increases effects of inhibitory GABA ligand)
where are GABA receptors found?
- usually found on the cell body (axosomatic)
how do GABA receptors work?
- excitiation from dendrites due to activation of glutamate receptors regulated by GABA in the cell body
- without GABA neurons would fire action potential continuously under the influence of glutamate
what is synaptic integration?
inhibition and excitation together
what can synaptic integration do?
- have different combinations which produce different effects
how can a ligand gated ion channel use synaptic integration?
- eg Na+/K+/Cl-
- direct regulation of membrane potential
how can a metabotropic receptor depended activation of 2nd messenger signalling channel use synaptic integration?
- eg cAMP
- regulation of channel or receptor number or activity by phosphorylase gene expression
how can a lNMDA receptor dependent activation use synaptic integration?
- eg Ca2+
- regulation of membrane trafficking and gene expression
how can diffusible retrograde signals secreted from post synapse use synaptic integration?
- eg cannabinoids, NO
- activation of metabotropic GPCRs or signalling enzymes to regulate channel activity
- released from the post synapses travel to the presynapse and regulate NT release
- endogenous cannabinoids - act on receptors normally in your brain
- diffuse across synpase and interact with a G protein receptor
