Action Potentials Flashcards
What are the 3 kinds of communication between neurons?
Modulatory, inhibitory and stimulatory
Where can neurones synapse?
With one or more neurones on their axons, cell bodies, dendrites
Or with other cell types (e.g. muscle)
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
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
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
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)
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
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.
Give an example of a uniporter
GLUT-1
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.
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)
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
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)
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)
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
Give an example of a uniporter ion pump
Calcium ATPase
In the plasma membrane to decrease cytosolic calcium concentration
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
Give an example of an antiporter ion pump
3Na+/2K+ pump (pumps Na+ out and K+ into the cell)
What kind of transport are transporters allowing?
Secondary active transport
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
- Axon hillock contains high levels of VG Na+ channels
- Depolarisation opens the Na+ channels
- Na+ enters approaching Na+ equilibrium
- VG K+ channels open and lead to efflux of K+ and hyperpolarisation (more –ve)
- 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?
- 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
