Lecture 8 - Part 2 - Synapses and drugs Flashcards by Maryam

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

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Where does action potential transmission occur

In axon of pre - synaptic neuron

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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

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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

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What is synaptic cleft

Gap - separates pre/post membrane

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What is the more common synapse

Chemical

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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

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What is electrical synapse/gap junction

Proteins of one cell joined to protein of another cell = ionic continuity between cells

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How are adjacent cells joined in electrical synapse

Via gap junctions

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What do gap junctions allow

Ionic continuity between cells

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What does electrical synapses allow

Action potential directly from one neuron to post synaptic neuron

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Advantage of electrical synapse

Fast - no release of neurotransmitter

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Disadvantage of electrical synapse

Inflexible - can’t modify action potential

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Where are electrical synapses used

Heart - contracts quickly - dont have to change it

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What is synaptic transmission

Neurons join each other at synapses - action potential transferred

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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

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Structure of a chemical synapse

Mitochondria - energy ( PRE )
Vesicles (containing neurotransmitter) ( PRE )
Synaptic cleft ( gap )
Post synaptic receptors ( POST ) -

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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.

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Single post synaptic cell receiving info from neurons

A single post-synaptic cell can receive synaptic input from several thousand pre-synaptic neurons

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What do muscle cells conduct action potentials like

Nerve cells

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What is a neuromuscular junction

Nerve cell and muscle cell

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What is neuromuscular junction also called

Motor endplate

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How many neurons does each muscle fibre receive input from

Only one

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What is found in pre - synaptic region

Vesicles
Mitochondria
Synaptic cleft

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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