Lecture 8 - Part 2 - Synapses and drugs Flashcards
What happens at a synapse
- Information is transferred from one neuron to another, neurons join each other here
- Pre synaptic neuron attaches to post synaptic neuron at synapse
Where does action potential transmission occur
In axon of pre - synaptic neuron
What are the 2 alternatives to explain the process of synaptic transmission
Electrical - potential goes directly from one cell to next- action potential jumps from one neuron to another
Chemical - chemical is released by presynaptic neuron - acts on postsynaptic neuron
Evidence for chemical synaptic transmission
Synaptic cleft (30-40 nm) - too wide for action potential to jump across. If neurons arent touching each other i.e. there’s a gap, it can’t be electrical transmission
- Synaptic delay (0.5-0.8 msec) when stimulate pre synaptic neuron, theres a delay before postsynaptic response
- Classic Otto Loewi experiment
What is synaptic cleft
Gap - separates pre/post membrane
What is the more common synapse
Chemical
What is Classic Otto Loewi experiment
Connected heart in beaker to another heart in 2nd beaker - only if chemical released - neurotransmitter
Attached to 1st heart was a nerve - vagus nerve - stimulate this = heart slow down
What is electrical synapse/gap junction
Proteins of one cell joined to protein of another cell = ionic continuity between cells
How are adjacent cells joined in electrical synapse
Via gap junctions
What do gap junctions allow
Ionic continuity between cells
What does electrical synapses allow
Action potential directly from one neuron to post synaptic neuron
Advantage of electrical synapse
Fast - no release of neurotransmitter
Disadvantage of electrical synapse
Inflexible - can’t modify action potential
Where are electrical synapses used
Heart - contracts quickly - dont have to change it
What is synaptic transmission
Neurons join each other at synapses - action potential transferred
What is difference between electrical and chemical synapse
Electrical: Gap junction - very quick - straight from pre to post membrane
Chemical: Slow - due to release of transmitter
Structure of a chemical synapse
- Mitochondria - energy ( PRE )
- Vesicles (containing neurotransmitter) ( PRE )
- Synaptic cleft ( gap )
- Post synaptic receptors ( POST ) -
What are the initial stages of chemical synaptic transmission
- The arrival of an action potential at pre - synaptic neuron causes influx of Ca+ as Ca channels open
- This causes the vesicle with neurotransmitter to migrate towards the presynaptic membrane
- Here it releases its content via exocytosis
- Neurotransmitter diffuses across the synaptic cleft (down its concentrationtransmitter gradient) and binds to postsynaptic receptors.
Single post synaptic cell receiving info from neurons
A single post-synaptic cell can receive synaptic input from several thousand pre-synaptic neurons
What do muscle cells conduct action potentials like
Nerve cells
What is a neuromuscular junction
Nerve cell and muscle cell
What is neuromuscular junction also called
Motor endplate
How many neurons does each muscle fibre receive input from
Only one
What is found in pre - synaptic region
- Vesicles
- Mitochondria
- Synaptic cleft
Recording from 2 points on a muscle fibre following neural stimulation
- Motor neuron stimulated
- 2 electrodes on muscle cell - action potential recorded
What does action potential long way from nerve show
Regular action potential
What does action potential close to stimulus show
Little and bump = EPP
What is Endplate potential ( EPP)
Triggers action potential ( by depolarisation - Na = inside neuron
How can action potential in a muscle fibre be abolished
By curare
What happens when action potential in a muscle fibre is abolished
Endplate potential is revealed - triggers action potential
What is curare
Drug stopping action potential in muscle cells - abolished action potential leaving EPP only
What happens at neuromuscular junction
Ach binds to the receptors on the sarcolemma, opening sodium channels = influx of Na+
What does influx of Na+ cause
EPP
If threshold reached- action potential
Summary of EPP
Action potential - releases AcH - AcH binds to protein receptor which changes shape - opens ion channel - Na+ into neuron - small depolerisation - EPP - action potential
What chemical is found in vesicles at pre - synaptic neuron
AcH
What happens when AcH is released
EPP = small depolarisation - triggered action potential on muscle - contracts
What does EPP result in
Action potential
What causes receptor to change shape
Binding of neurotransmitter
What determines whether a postsynaptic cell will fire
EPSPs and IPSPs sum
How much excitation it has - sometimes they fire, sometimes they dont
What is excitatory postsynaptic potential ( EPSP)
Small depolarisation in post synaptic cell = opens Na+ channels but not enough to trigger action potential
What is inhibitory postsynatpic potential ( IPSP )
Small depolarisation, not enough to trigger action potential
What happens If both IPSP and EPSP added together
threshold reached - action potential
Ionic mechanisms of IPSP
Open Cl- channels - INTO neurone
Open K+ channels - OUT of neurone
Post synaptic cell negative
Hyperpolarise postsynaptic cell
Ionic mechanisms of EPSP
Open Na+ channels = Na+ into neurone = depolerisation = action potential
Inside negative
What happens when neurotransmitter binds to ion channel
Ion channel changes shape = opens = ion flows -
How can neurotransmitters alter ionic permeability
Binding directly onto postsynaptic membrane protein receptors.
e.g.cation channel is normally shut, but when Ach binds to it, it changes shape allowing the passage on Na+ and K+.
What is the mode of action of transmitters
-Direct activation of an ionic channel
-Use of a secondary messenger (i.e. cGMP,
phospholipase C etc.)
What are the mechanisms of transmitter inactivation
- Diffusion
- Reuptake
- Enzymatic breakdown
How does diffusion inactivate transmitter
- Falls of and diffuses
How does reuptake inactivate transmitter
- Pre-synaptic neuron sucks it back up
How does enzymatic breakdown inactivate transmitter
Enzymes in synaptic cleft break down neurotransmitter into component parts
e.g. acetlycholinesterase
Why inactivate transmitter
Neurotransmitter can’t stay bound - get rid of it - or it overstrimulates postsynaptic neuron
Summary of events at a chemical synapse
- Arrival of potential causes influx of calcium
- Calcium causes vesicles containing neurotransmitter to migrate to presynasptic membrane
- Transmitter released via exocytosis
- Transmitter migrates to postsynaptic receptors
- Activation of receptors causes change in postsynaptic ionic permeability
- Neurotransmitter inactivation
- IPSP, EPSP (EPP)
Examples of neurotransmitters
Neuroactive peptides - short chains of amino acids
- Nitric oxide - gas - dilation of blood vessels
Colocalisation of more than one neurotransmitter to a single neuron
Neurons have many neurotransmitters - in single pre - synaptic cell - releasing different ones at different times
What are 2 basic types of Acetylcholine receptor
Nicotinic
Muscarinic
Nicotinic receptor
- Occur at neuromuscular junction = open Na+ channels = are therefore excitatory
Muscarinic receptor
Occur on heart = open K+ and Cl- channels = inhibitory
Heart slows down
What does receptor determine
Whether you get ISP or ESP
Examples of diseases due to defects in synaptic transmission
- Parkinson’s - lack of dopamine
- Schizophrenia - too much dopamine
- Myasthenia gravis destruction of Ach receptors
- Depression- low levels of serotonin and nor-adrenalin
What are drugs that enhance effectiveness of a neuron
Agonists
What are drugs that suppress specific neurons
Antagonists
What is L - dopa
Precursor for dopamine synthesis to alleviate the symptoms of Parkinson’s
What happens in botox
Botulinum toxin cleaves synaptic vesicles
What happens in Atropine
Ach receptor blocker
Dilates pupils - muscle of iris
Ach can’t bind to receptor = pupil can’t restrict
What is prozak
Serotonin reuptake blocker
What happens during transmission
Action potential is transferred
Why can’t you use dopamine instead of L - dopa
Dopamine is big = can’t get into brain
How does L dopa work
Smaller
Make dopamine - gets into brain
Astrocytes = blood brain barrier
How does botox work
Cosmetic industry
Relaxes skeletal muscle and muscles of face
Only lasts 6 weeks
Squinting - use in eye, relax lateral rectus muscle - inject with botox = relax = eye points forwards
