Biophysics Flashcards
What is equilibrium potential for an ion ?
It is the state at which the ions are in a state where not further changes are possible
What happens when ions cross a membrane to move down their concentration gradient ?
They produce a potential difference closer to their equilibrium potential
What is an electrochemical potential ?
It is when there is no net movement of ions because the electrical forces completely balance the diffusional forces
What does the sodium-potassium ATPase pump do ?
It maintains the gradient across the membrane at rest
It pumps against the concentration gradient so it uses ATP. It pumps 3 sodium ions out for every 2 potassium ions in
What are ion channels ?
Integral membrane proteins that are selectively permeable to certain ions
Conduct small ionic currents
What are transporters/exchangers ?
Integral membrane proteins which either transport or exchange ions across the membrane
Don’t have a pore so they don’t usually conduct ionic current
What are ion pumps ?
Integral membrane proteins
Transport ions against their electrochemical gradient
Requires ATP
How do voltage gated channels ?
They are very selective due to their gating mechanisms
The gate opens/closes based up the potential
The pore of these channels have selectivity filters enabling passage of specific ions
Gate is connected to a voltage sensor which is sensitive to changes in voltage
Gate opens upon conformational changes in the channel
Explain the potassium channel selectivity filter ?
In their pores they have a sequence which is an acidity filter and is highly conserved - TVGYG
Potassium ions are surrounded by water molecules making it easier to diffuse in the cytosol
The acidity filter in the pore mimics the hydration of the potassium ions so their for the oxygen moieties can interact and allow potassium to diffuse through the channel easily.
Sodium also has water molecules surrounding it but because sodium is a smaller molecule the woxygen moieties are too far away to interact so sodium doesn’t pass through the potassium channel
What are the 2 gates present in sodium channels ?
M gate - activation gate which opens upon depolarisation to allow sodium ions to pass through the channel
H gate - inactivation gate which activates just after the pore has been open to plug the pore so no more sodium ions can pass through it remains activate for a while causing he refractory period so there is no more sodium influx
What is the voltage-clamp technique ?
1- an electrode is inserted into the neurone and this measures the membrane potential across it. This electrode is connected to a voltage clamp amplifier
2- voltage clamp amplifier compares the membrane potential of the neuron with the desired membrane potential
3- if the membrane potential in the neuron is different from the desired membrane potential then the clamp amplifier injects current through another electrode
4- using a current measured the current which is injected to get the membrane potential to the desired potential is recorded
What does the voltage clamp technique indicate ?
It tells us how the membrane potential influences current
It is used to clamp the voltage and then record he effects on the current
What are reversal potentials ?
It is the point at which the potential of the end plate current reverses
What is the current clamp technique ?
In this technique the current flowing across the membrane is controlled so the voltage can be recorded
Useful for looking at actions potentials
When an action potential occurs why doesn’t the membrane potential reach the equilibrium potential of sodium ?
Because the sodium channels inactivate very quickly - their effects are transient
What is the role of sodium channels in the action potential ?
They are voltage gated and open upon depolarisation
Once they open they enable and influx of sodium ions and this causes more sodium channels to open, the explosive influx only occurs if the threshold is reached - push the membrane potential towards their equilibrium potential but inactivate rapidly
They remain inactivate during the refractory period preventing any further action potentials occurring
They inactivate after about 1-2ms
What is the role of the potassium channels in the action potential ?
The voltage potassium channels also open at depolarisation but at a more positive potential compared to sodium- they have slower kinetics that sodium channels
This delayed opening of the potassium channels is fundamental in the repolarisation of the cell
At rest some voltage gated potassium channels are open and leak potassium channels are open and this is important for maintaining the membrane potential at rest
What are calcium-activated potassium channels ?
There are some potassium channels which react to the internal calcium concentration- they contribute to repolarisation of the cell
These channels are often in cells which contain the voltage calcium channels which contribute to depolarisation
These channels remain open longer than voltage gated potassium channels which is why they cause he undershoot of the action potential=afterhyperpolarsation
Why is an action potential normally unidirectional ?
Because the previous region that was depolarised can’t be depolarised straight away again because it is in its refractory period
In the CNS why are action potentials generally generated in the axon initial segment ?
Because this is where there is he highest concentration of sodium channels
What is saltatory conduction ?
It is the means of passing on an action potential in myelinated neurones
The action potential jumps from each node of ranvier to the next because the nodes contain the high concentration of ion channels
What is driving force equal to ?
The membrane potential minus the equilibrium potential of the ion
Why are calculated reversal potentials always different to the real life reversal potentials ?
They are never the same as the calculated potentials because there are leak channels present in the membrane which allow the passage of ions
What are phased neurones ?
Fire a burst of transient activity and then shut down
What are tonic neurones?
Neurones which constantly fire
What are accommodating neurones ?
Initially fire at a high frequency but then get slower and slower until they stop
What are spontaneous active bursting neurones ?
These are pacemaker neurons
They don’t require an external stimulus
Neurone oscillates without an external input and then shuts down automatically
What is the patch-clamp technique ?
Enables recordings of electrical activity of a neurone
Using a glass electrode and placing it ins reservoir of cells, the membrane of a cell can be sucked into the electrode by applying a negative pressure
The resistance between the membrane and the electrode is so tight it creates a gigs ohm seal which ensures leak current is tiny
It enables the recording of activity of a single channel
What toxin can be used to block sodium currents ?
Tetrodotoxin-it blocks sodium channels
What toxin can block potassium currents ?
Tetrammonium - blocks potassium channels
What is the benefit of blocking the sodium and potassium channels independently ?
It enables the ability to see the effects of current and membrane potential caused by each ion separately. It can show the threshold for opening of each of the ion channels
Sodium channel threshold is about -50mV
Potassium channel threshold is about -20mV
What are outwardly rectifying potassium channels ?
There are 2 types
- non inactivating channels which stay open as long as depolarisation occurs
- inactivating channels which open at depolarisation and close at hyper polarisation
What are inwardly rectifying potassium channels ?
They open at hyper polarisation and close at depolarisation
They do not participate in depolarisation of action potentials
What are depolarising activated non inactivating potassium channels ?
They are an outwardly rectifying current
They are referred to as M current
What are depolarising activated inactivating potassium channels ?
They are outwardly rectifying current
They are known as A current
What are depolarising and calcium activated potassium channels ?
They are sensitive to the intracellular concentration of calcium and also voltage
They are known as BK channels
They change the shape of the action potential
What are cyclic nucleotide activated cation channels ?
These are depolarising channels which are non selective to cations
They are called H current
What is an example of an inward rectifying potassium channel ?
GIRK channel - G protein inwardly rectifying potassium channel
These open by hyper polarisation
What are the properties of the M channel ?
They slowly activate
They are non-inactivating so they are too slow to cause repolarisation
Important at maintaining the resting membrane potential
Remains open as long as depolarisation is occurring
Has a low threshold of about -60mV so it’s contributes to the leak channels
It’s classed as an accommodating neurone
What is an example of an M channel activator and what is its purpose ?
Retigabine
It is an anti-epileptic drug which enables the M current so less aps are fired
What is an example of an M channel inhibitor ?
XE991
It causes the neurone to firing tonically
What neurotransmitter inhibits M channels and what is the consequence ?
Acetylcholine
It targets M channels and inhibit its current so neurone remains excited
What are the effects of acetylcholine on muscarinic receptors ?
When it binds to M 1 receptors it’s linked to Gq protein which inhibits M current and caused excitation
When it binds to M 2 receptors it’s linked to Gi proteins which causes GIRK activation causing inhibition of the neurone
What happens when chloride channels are opened in mature neurones ?
They have a low intracellular chloride concentration
They have more KCC2 channels so they constantly extrude chloride ions
What happens to chloride when chloride channels are opened in an immature neurone ?
They have a high intracellular chloride concentration
They have more NKCC1 channels which is why they have a high intracellular chloride concentration
What happens when GABA binds to mature neurones ?
Causes hyperpolarisation
What happens when GABA binds to immature neurones ?
It causes depolarisation
