Action Potentials Flashcards by Maria Sasakis

What are the 3 kinds of communication between neurons?

Modulatory, inhibitory and stimulatory

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Where can neurones synapse?

With one or more neurones on their axons, cell bodies, dendrites

Or with other cell types (e.g. muscle)

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Name the 2 different types of synaptic pathways

Convergent: More than one neurone synapse (can be a mix of excitatory and inhibitory) with a neuron

Divergent: One neurone synapses with multiple other neurones

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Describe the general path inputs take after reaching the post synaptic neurons

Inputs reach the soma –> axon hillock determines whether the action potential will go down axon –> AP travels down axon–> synapse with another cell

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What is the resting membrane potential of neurones and how is it maintained?

-60-70mV

Lipid bilayers that make up membranes are essentially impermeable to ions

However at rest there is an imbalance of various ions across the plasma membrane

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List the relative concentrations of the most important ions in the neuron and how they are kept at this concentration

Na+ is higher extracellularly than intracellularly: 3Na+/2K+ ATPase

K+ is lower extracellularly:3Na+/2K+ ATPase allows K+ to go into the cell and K+ channel allows it to go out

Ca2+ is higher extracellularly:Ca2+ ATPase
and 3Na+/Ca2+ antiporter

Cl- is higher extracellularly: K+/Cl- transporter (symporter)

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What are the 3 kinds of ion transporters? Explain

Uniporters: Transport one species down its concentration gradient

*next two utilise one species moving down gradient to drive the other up its gradient

Symporters:2 species in same direction
Antiporters: 2 species in opposite directions

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Explain how the uniporter works

It is based on random conformational change to transporter. If concentration of X is higher on one side more will bind that side. More X is released on the side of lower conc.

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Give an example of a uniporter

GLUT-1

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Explain how a symporter works

(Assume X goes down its gradient and thus drives Y)

X binds
The affinity for Y increases
Y which is in low concentration binds
Conformational change og transporter
X is released
Affinity for Y decreases
Y is released in area of high conc.

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Give an example of a symorter

Glutamate dopamine transporters (DAT) : neurotransmitter reuptake at the nerve terminal (takes Na into the cell down its gradient and uses this to drive glutamine against its gradient)

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Explain how antiporters work

(Assume X goes down its gradient and thus drives Y)

X binds
The affinity for Y decreases
Y is released
Transporter changes conformation
X is released
Affinity for Y increases
Y binds
conformational change

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Give an example of an antiporter

VMAT2 (vesicles monoamine transporter 2): small synaptic vesicle neurotransmitter uptake for dopamine

(Uses the gradient of H+ to pump dopamine into the vescicle)

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How do ion pumps differ from transporters?

They use ATP hydrolysis to influence the binding of the ion at low concentrations and release into areas of high conc (aka. up their conc. gradient)

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How does an ion pump uniporter work?

ATP is hydrolysed causing the affinity for X to increase
X binds
Conformational change
Affinity for X decreases
X released in area of higher conc

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Give an example of a uniporter ion pump

Calcium ATPase

In the plasma membrane to decrease cytosolic calcium concentration

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How does an antiporter pump work?

Transporter is dephosphorylated
Affinity for Y decreases while that for X increases
Y released in region of high conc
X binds in region of low conc
Phosphorylation leads to conformational change and a reversal in affinities
X is released and Y binds
Dephosphorylation induces conformational change

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Give an example of an antiporter ion pump

3Na+/2K+ pump (pumps Na+ out and K+ into the cell)

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What kind of transport are transporters allowing?

Secondary active transport

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Why does lack of ATP affect the cell so much?

Transporters use gradients set up by ATPase pumps for secondary active transport so not only the pumps but also the related transporters will cease to function

Define ion channels

They are pores that:
Allow free movement of ions down their gradient.

Fast acting allowing many ions to move, but not as specific with regard which ions move as transporters and pumps

Give examples of 2 gated ion channels

Voltage gated i.e. VG Na+ channel open upon depolarisation of axon

Ligand gated i.e. NMDA glutamate receptor, opens when glutamate bound, allows in Na+ and Ca2+

What do transporters, pumps and channels have in common?

These are proteins that span the membrane and allow molecules/ions to cross the membrane

How are transporters and pumps similar

Allow the stoichiometric (ratios) movement of ions /molecules

Are slow acting

Can move molecules against their gradient

Are relatively specific

What is the all or nothing law?

Depolarisation (more +ve) is required to reach a threshold level for an action potential to fire Above -50mV

Describe how an action potential is generated in an axon hillock

1. Axon hillock contains high levels of VG Na+ channels 2. Depolarisation opens the Na+ channels 3. Na+ enters approaching Na+ equilibrium 4. VG K+ channels open and lead to efflux of K+ and hyperpolarisation (more –ve) 5. Ion balance recovers towards E K+

Do neurons express many different VG ion channels?

Yes 8 different VG Na+ channels Several different VG K+ channels 5 different VG Ca2+ channels

Why do neurones express so many VG ion channels

In order to increase the ability to regulate neural activity

Why does the action potential have directionality?

Because of the absolute refractory period

Why is there an absolute refractory period?

After a VG Na+ channel is activated, upon repolarisation it becomes inactive and does not allow ions through during depolatisation

Why are VG Na+ channels a good target for antiepileptics?

Because they control the refractory period

Compare naked axons to myelinated ones

Naked axons have poor electrical properties AP would die out except for the VG Na+ channels along the axon Propagation is slow as AP jumps from channel to channel

What does myelin do?

Insulates the axons through decreasing leaks Na+ channels are at nodes and propagate AP from node to node instantly, much faster They also help nerve regeneration

In what diseases is demyelination seen?

MS and peripheral nerve diseases

When do Schwann cells develop?

In the embryo

Why are teens so fast at reacting to things?

The Schwann cells continue to increase their wrapping around the axon throughout childhood, peaking in adolescence

Describe the structure of a Schwann cell

As the cell surrounds the axon, the nucleus and other organelles are pushed to the outer side of the cell (forming the neurollema) The inner wrapping is the myelin sheath

How do AP in unmyelinated neurones differ compared to myelinated ones?

Unmyelinated is slower because APs continue down the axon as the Na+ entering the axon diffuses to the neighboring areas and causes depolarisation (leading to opening of Na+ channels and then repeat) In myelinated: Diffusion of Na+ occurs through the area that is myelinated until it reaches a node of Ranvier and then the Na channels open there once –60mV threshold is reached (thus AP move from node to node)

Why are channels and transporters in neurones interesting to us?

- mutations can cause disease - toxins (e.g. snake and fish toxins) can be fatal - can be a target for therapy

What part of the brain is mainly affected by channelopathies?

Cerebellum

Give 3 examples of chanellopathies and their causes

Ataxias: - Cerebrospinal ataxia 6 (SCA 6) VG Ca2+ channel (CACNA1) - SCA13 - VG K+ KCNC3 Epilepsy: -VG Na+ channel

What is tetrodtoxin and how does it work?

Produced by puffer fish and frogs Inhibits VG Na+ channels and can be fatal

What can be target proteins for neuropharmacological drugs?

Proteins involved in : - Action potential - NT regulation - Neurotransmission

What are the strategies to inhibit abnormal neuronal discharge in epilepsy?

1. Inhibit voltage gated sodium channels | 2. Increase GABA neurotransmission (GABA is inhibitory NT)

What kind of neurotransmitter is GABA?

Inhibitory

Why do we have to be careful with Na+ channel blocking?

It can be fatal if all the channels are blocked

What is the solution to the problem of Na+ channel blocking epilepsy drugs (and how they might kill you if too potent)?

Use a drug which blocks the inactivated phase of the VG Na+ channel. Inactivation of the channel is key to refractory period of neurons, and to understanding the mechanism of VGSC blockers in epilepsy Very active neuron = many inactivated channels, so binding the drug to inactivated version can inhibit only to too reactive ones

Name 3 antiepileptics which inhibit VGSC

Carbamezapine Phenytoin Lamotrigine