Introduction Flashcards
How many prescriptions are CNS active
- 1/6
Describe briefly what happens at a synapse
- depolarise presynaptic nerve terminal
- VG calcium channels open
- Calcium enters presynaptic cell
- Causes vesicles containing neurotransmitter to fuse with the membrane
- Release the neurotransmitter which bind and activate postsynaptic receptors- ligand gated ion channel
What is a ligand gated ion channel
- Protein that is a pore
- Cation channel- sodium or potassium ions to permeate through the channel and into the cell
- Carry with them positive charge
What are features of a nerve cell
- dendrites
- axon- myelinated
- cell body
- nerve terminals- synapse onto other nerve cells
- electrically stimulated- can lead to generation of action potential in cell body and causes release of neurotransmitter
What happens at the dendrites
- information gathering parts of the cell
2. where other nerve cells synapse to it
What are ionotropic receptors
- Also called ligand gated ion channels
- Ionotropic receptors are membrane-bound receptor proteins
- respond to ligand binding by opening an ion channel and allowing ions to flow into the cell, either increasing or decreasing the likelihood that an action potential will fire.
Describe what happens with excitatory synapses of ionotropic receptors
- Transmitter depolarizes and excites
- Inward positive current e.g. Na+ ions move into cell
- Excitatory postsynaptic potential (EPSP)
Give 3 examples of excitatory neurotransmitters
- Glutamate
- Aspartate
- Acetylcholine (nicotinic)
What is excitatory and inhibitory synapses
- Signals sent across excitatory synapses increase the activity of the receiving neuron
- signals sent across inhibitory synapses reduce neuron activity
Describe what happens with inhibitory synapses of ionotropic receptors
- Transmitter hyperpolarizes and inhibits
- Inward negative current e.g. Cl- move in
- Inhibitory postsynaptic potential (IPSP)
Give 3 examples of inhibitory neurotransmitters
- GABA (gamma-amino butyric acid)
2. Glycine
What are the 4 different types of synapse
- Axo-somatic- axon onto cell body
- Axo-dendritic- axon to dendrite
- Dendro-dendritic- dendrite to dendrite
- Axo-axonic- axon to axon
What is the difference between temporal and spatial summation
- Spatial summation occurs when multiple presynaptic neurones together release enough neurotransmitter (e.g. acetylcholine) to exceed the threshold of the postsynaptic neurone.
- Temporal summation occurs when one presynaptic neurone releases neurotransmitter many times over a period of time.
Why is the CNS so complex
- Neurones are highly complex structures
- Multiple synapses on each neurone
- Several different types of synapse
- Multiple transmitters
- Multiple receptors
- Multiple messenger systems
- Neurones interconnected in complex networks
Why is Ca2+ a neurotransmitter
- Present in presynaptic neuron
- Ca2+ dependent release in response to presynaptic depolarisation
- Postsynaptic receptors present
What are the 4 types of neurotransmitter
- Amine
- Amino acids
- purines
- peptides
What can G-protein coupled receptors be linked to
- Linked to ion channels- K+, Ca++
2. Linked to enzymes- adenylyl cyclase, phospholipase
Give 3 examples of G-protein coupled receptors
- Adrenaline
- Noradrenaline
- Dopamine
What are some complications of the complexity of CNS
- Multiple possible sites for dysfunction
- Subtle variations in phenotype of disorders
- Diagnosis problems
- Multiple sites of possible intervention
- Drugs rarely selective
- BUT multiple possible drug targets even for a single neurotransmitter
What are the sites of action of CNS drugs
- Substrate transporter
- Synthesis pathway
- Vesicular transporter
- Vesicular movement
- Release process
- Postsynaptic ionotropic receptors
- Postsynaptic GPCR
- Second messenger systems
- Uptake transporter
- Enzymatic degradation
- Presynaptic receptors
- Membrane ion channel
What are drug actions complicated by
- Uncertainty over disease aetiology
- Multiple possible sites of action
- Non-specificity of drugs
- Reactive changes within networks
- Adaptive changes at synapses
- Tolerance and dependence