axonal and synaptic neurotransmission Flashcards
basic components of a neuron
o Dendrites
o Cell body/soma
o Axon
o Presynaptic terminals
name 4 different types of neuron
multipolar
bipolar
Pseudo-unipolar
unipolar
what causes multiple Sclerosis
failure of axonal transmission
myelin lost
symptoms of multiple sclerosis
o Eye movement – uncontrolled o slurred speech o Paralysis o Tremor o Lost co-ordination o Weakness o Sensory issues e.g. numbness
describe the axon in the resting state
- Result is NA+ high concentration outside but with both forces pushing in
- Membrane and pump resists Na+ inward movement
- K+ & Cl- can move backward and forward across membrane so reach steady state determined by opposing forces of diffusion and electrostatic pressure
- Some sodium leaks back in but is expelled by the pump
what is the charge of the neuron in the resting state
-70mV
describe how an action potential arises
1) Neurotransmitters activate receptors on dendrites / soma
2) Receptors open ion channels
3) Ions cross plasma membrane, changing the membrane potential
4) The potential changes spread through the cell
5) If the potential changes felt at the axon hillock are positive (+mV), and large enough, an action potential is triggered
what do excitatory neurotransmitters do?
depolarise the cell membrane
increases probability of an action potential being excited
cause an Excitatory Post Synaptic Potential (EPSP)
what do inhibitory neurotransmitters do?
hyperpolarise the cell membrane
decreases probability of an action potential being elicited
cause an Inhibitory Post Synaptic Potential (IPSP)
what is axonal transmission (short)
transmission of info from location A to B
what is synaptic transmission (short)
integration/processing of info and transmission between neurons
what are the two types of summation
Spatial summation – stimulation of several neurons
Temporal summation – similar time frame, may or may not summate
summary of synaptic transmission
1) Neurotransmitter release
2) Calcium ion channels open when action potential reaches pre-synaptic terminal
3) Ca++ ions cause vesicles to move to release sites – fuse with the cell membrane – and discharge their contents
4) Transmitter substance diffuses across synaptic cleft
5) Attach to receptor sites on post-synaptic membrane
when do EPSPs begin to depolarise the cell membrane
-60mV
when to voltage-gated sodium channels close and potassium open
+30 mV
propagation of action potential - non-myelinated
- Signal loss due to lack of insulation –could be overcome by continual opening of next ion channel
- But SLOW due to time to activate each channel.
- Mainly short axon interneurons
saltatory conduction
- Decremental conduction between nodes (but ‘re-boosted’ each time)
- But very fast along axon.
- Most CNS neurons
neurotransmitter would remain active in synapse if it wasn’t for:
- Enzymatic Degradation – acetylcholinesterase (Novichok inhibits this)
- Reuptake
Novichok
- inhibiting breakdown of a neurotransmitter means it will stay active in the synapse
- So it will continue to have whatever effects it has, long after these would normally be terminated
symptoms of Novichok
- Excessive activation of muscles (convulsions) initially
- Subsequent paralysis as muscle cannot continually contract
- Failure of heart muscles (heart failure)
- Failure of muscles controlling respiration (asphyxsiation/drowning)
- Failure of muscles in eye (pupils constricted / paralysis)
- Failure of skeletal muscles (paralysis)
- Failure of muscles of digestive tract (vomiting/diarrhoea)
treatment of Novichok
- Atropine is an ACh receptor blocker – but doses needed to be effective very high (side effects)
- Drugs which can re-activate AChE may also be administered
- Usually intensive life-support required (due to cardiovascular effects)
- Long-term damage of neuromuscular function probable
5 fundamental processes of synaptic transmission: often targeted by drugs
- Manufacture – intracellular biochemical processes
- Storage – vesicles
- Release – by action potential
- Interact with post-synaptic receptors – diffusion across the synapse
- Inactivation – break down or re-uptake
Fast neurotransmitters – short lasting effects
o Acetylcholine (ACh) o Glutamate (GLU) o Gamma-aminobutyric acid (GABA)
Neuromodulators – slower timescale
o Dopamine (DA) o Noradrenalin (NA) (norepenephrine) o Serotonin (5HT)
how do local anaesthetics work (Procaine and lignocaine)
o Na+ channels blockers-particularly well absorbed through mucous membranes - ’EMLA cream’
o Blocks progress of action potential
Acetylcholine (Ach)
Transmitter at the neuromuscular junction, also used widely in brain and spinal cord Affected by: o Cigarettes (nicotine - agonist) o Poison arrows ( curare - antagonist) o Spider toxins (black widow - release) o Nerve gas (WW-I – blocks break-down)
Noradrenaline (NA)
Transmitter in peripheral (heart) and central nervous systems – diverging architecture in brain
Affected by:
o Antidepressant drugs (Imipramine – blocks re-uptake)
o Antidepressant drugs (MAO inhibitors – block break-down)
o Stimulants (Amphetamine – increases release and blocks re-uptake)
Dopamine (DA)
Important transmitter in basal ganglia – diverging architecture
Affected by:
o Antipsychotic drugs (Chlorpromazine – receptor blocker)
o Stimulants (Amphetamine/cocaine – increase release and block re-uptake)
o Anti-Parkinson drugs (L-DOPA increases manufacture
Serotonin (5-HT)
Diverging projections in the brain – innervating many structures
Affected by:
o Antidepressant drugs (Prozac – serotonin re-uptake inhibitor – SSRI)
o Hallucinogens (LSD –5HT receptor agonist)
o Ecstasy (MDMA – neurotoxic ?)
Hallucinogenic drugs
- Hallucinogenic drugs include LSD, Magic Mushrooms, Ketamine
- They mimic serotonin, and can activate numerous different serotonin receptor subtypes
- But the hallucinogenic effect itself appears to be specifically related to the way they target the serotonin ‘2a’ receptor (5-HT2a)
Gamma-aminobutyric acid (GABA)
Main inhibitory transmitter
Affected by:
o Anti-anxiety drugs (benzodiazepines - valium – inhibitory effect at GABA receptors
o Anticonvulsant drugs (benzodiazepines – see above)
o Anaesthetics (Barbiturates – potentiate the effect of GABA
Problems for drug design
• A region of the brain engaged in a particular function uses several neurotransmission systems e.g. basal ganglia: Glutamate, GABA, Dopamine, Acetylcholine, Substance P, Enkephalin
• Regions of the brain engaged in different functions use the same neurotransmission systems o Glutamate o GABA o Acetylcholine o Serotonin o Dopamine/Noradrenali This is why we have side effects:
