Chemistry and physiology of the synapse Flashcards
Axodendritic synapse
A synapse between the axon of a neurone and the dendrite of the other neurone.
Axosomatic synapse
A synapse between an axon and the body of the neurone (soma).
Axoaxonic synapse
A synapse junction between an axon terminal of a neurone and another axon terminal of a different neurone.
Structure of a presynaptic terminal [5]
Synaptic bouton- the presynaptic axon terminal.
Synaptic cleft- The small space between pre and post synaptic neurone.
Synaptic vesicles- contains neurotransmitters.
Secretory granules- organelle that packages hormones/ neuropeptides for secretion.
Active zone- site of neurotransmitter release
2 responses to neurotransmitters during synaptic transmission
- Excitatory or inhibitory neurotransmission.
- Membrane of the post synaptic cell becomes slightly depolarised of hyper polarised. - Neuromodulation- alters pre-cell from releasing neurotransmitters or post-cell from responding.
Neurotransmitter {4}
- Made by a neurone
- Present and released by presynaptic terminal to cause a defined effect in postsynaptic neurone/ effector organ.
- Mimics the action of endogenously released transmitter when administered exogenously.
- Has a mechanism to remove it from synaptic cleft.
Events of a synapse transmission
- NT made and stored in vesicles.
- Action potential reaches presynaptic terminal and depolarises it.
- Voltage gated Ca2+ channels open and causes Ca2+ to flow into the terminal.
- Influx of Ca2+ causes vesicles with NT to fuse with Pre-synaptic membrane.
- NT released across synaptic cleft via exocytosis.
- NT binds to receptors on Post-cell membrane and initiates to opening/closing of channels.
- Influx of ions excites of inhibits postsynaptic potential and changes the excitability of the cell.
- NT remove by glial cell or enzymatic degradation.
- Vesicle is formed again from plasma membrane of presynaptic cell.
Ionotropic receptors
- Structure
- Examples
- Speed of action/ Functio
Receptors that form an ion channel.
- Contains a central pore for ions to flow.
- Contain a binding site for a ligand.
Examples:
- Glutamate receptors
- Nicotinic
- Serotonin
- Glycine
Action:
- Very quick compared to metabotrophic
- Binding of ligand causes conformational change in protein, which opens the channel
Variation of ionotrophic receptors
Can vary based on…
Kinetics
-The rate at which the NT binds.
Selectivity
- Specific to certain ions
Conductance
- Rate of flux for ion
All factors influence the action of the receptor.
Synaptic integration
The combination of all the changes in the membrane potential.
This considers the inhibitory and excitatory inputs of the cell and calculates the overall potential.
Ionotropic Glutamate receptor
- Function
- Types
Ion channel receptors that respond to glutamate as a ligand.
Types:
- AMPA
- NDMA
- Kainate
Metabotrophic receptors
- Function
- Examples
- Speed of action
Receptors that act using secondary messengers and are indirectly linked to ion channels.
- Cause a cascade of metabolic reactions intracellularly.
Example: G protein receptors
- Metabotrophic glutamate
- Dopamine
- Beta-adrenergic in the heart
- GABA beta
Speed of action:
- Slower than ionotrophic, requires intracellular changes..
AMPA receptors
- Function/ Type
- Agonist
- Antagonist
Ionotrophic glutamate receptors that fluxes Na+ and K+
- Faster than NMDA receptors
- Causes the early stage of EPSP.
Agonist:
- AMPA
Antagonist:
- CNQX
Kainate receptors
- Function/ Type
- Agonist
- Antagonist
Ionotrophic glutamate receptors that fluxes Na+ and K+.
- Faster than NMDA receptors
- Responsible for early EPSP.
Agonist:
- Kainate
Antagonist:
- CNQX
NDMA receptors
- Function/ Type
- Agonist
- Antagonist
Ionotrophic glutamate receptors that fluxes Na+, Ca2+ and K+
- Responsible for late EPSP, it is slow opening.
- Leads to active of enzymes and other intracellular events
- Its effect on neuroplasticity may be the mechanism for learning and memory.
Agonist:
NDMA
Antagonist:
APV
Mechanism of NDMA receptors
Non-selective ion channel that requires glycine as a co-factor.
Activity dependant synaptic modification:
- Contains Mg2+ plug that blocks the channel.
- This membrane has to be already depolarised (in the presence of glutamate) to release Mg2+ through electrostatic repulsion.
Its flux of ions causes a longer period of depolarisation.
- Ca2+ ions lead to activation of many enzymes which allows synaptic plasticity.
Phencyclidine
Also known as ‘angel dust’
Drug that competitively antagonises NDMA receptors
- Causes hallucinations similar to that in schizophrenia
MK801
Drug that non-competitively antagonises NDMA receptors
- Blocks channel pore
- Causes hallucinations
NDMA receptors and excitotoxicity
Excess stimulation by glutamate leads to excess flux of Ca2+
Leads to increased activation of digestive enzymes= cell damage and death
Seen in:
- Strokes
- Anoxia/ hypoxia
- Cardiac arrest
Metabotrophic glutamate receptor
mGluR
- G-protein linked receptors
- Either Gq or Gi
Group 1: Gq, mGluR1+5
Group 2: Gi, mGluR2+3
Group 3: Gi, mGluR4, 6, 7, 8
Gi receptors
G-protein receptor that inhibits cAMP cascade.
Binding of ligand causes dissociation of heteromeric G-protein.
Causes:
- Inhibition of adenylyl cyclase, cAMP and PKA production
Examples:
- Group 2+3 metabotrophic glutamate receptors
Gq receptors
G-protein receptors that activates PLC cascade.
PLC breaks down PIP2 into:
- DAG—> activates PKC
- IP3—> binds to ER membrane to release Ca2+ stores
D2 receptor
Gi receptor
- Inhibits cAMP pathway, in response to dopamine
Long term synaptic changes
Structural and biochemical recruitment of new receptors due to an alteration in gene transcription.
Allows for synaptic plasticity.
GABA receptors
Inhibitory receptors.
Ionotrophic= GABA alpha Metabotrophic = GABA beta
Short G-protein pathway
Does not involve a cascade of chemical intermediates.
Beta-gamma unit binds directly to K+ channels and causes them to open.
Examples:
- GABA beta
- Muscarinic heart receptors
Pre-synaptic receptor modulation
Autoregulation
- Receptor modulates the release of its own NT
- Example: tyrosine hydroxylase
Heteroregulation
- Receptor modulates the release of other NT it does not secrete.
- Ach with adrenergic receptors
Post-synaptic receptor modulation
Changing the firing pattern and activity, post-synaptically.
- Lingand gated
- G-proteins
Enzyme-linked receptor
Receptor linked to an enzyme
Example: Tyrosine kinase
- Activated by neutrophin
- Phosphorylates itself before doing so to other proteins
Membrane permeant signal molecules
Do not bind to extracellular receptors, but intracellular.
Example:
NO and guanylyl cyclase
