Resting and action potential Flashcards
What is diffusion?
Movement of a substance down its concentration gradient to establish dynamic equilibrium.
It is useful for transport over short distances.
It is a spontaneous process and no energy is required.
What is the electrical potential?
It is the charge gradient between two areas. It transmits information reliably and quickly over large distances.
e.g. it controls the entry of calcium into cells. Ca is important in releasing chemical signals so therefore can manipulate biochemical pathways: gene regulation, growth and death
What is flux?
It is rate of transfer of molecules
I.e. the number of molecules that cross a unit area per unit time (per m^2 per second)
When there is diffusion equilibrium, there is no net flux
What are the properties of ions?
Ions= charged molecules. Like charges repel, opposite charges attract.
What are the electrical properties of excitable cells?
Voltage= potential difference (volts) It is generated by ions to produce a charge gradient
Current (amps)- movement of ions per unit time due to a potential difference
Resistance (ohms)- barrier that prevents the movement of ions (i.e. the cell membrane). The permeability of the membrane is key to the resting potential
(v=Ir)
What are the 2 gradients associated with movement across the cell membrane?
- Diffusion (concentration) gradient
- Charge gradient
What is the convention in measuring resting membrane potential?
A reference electrode is placed outside the cell- this is the 0V level.
Another electrode is placed inside the cell. It measures a voltage difference that is negative with the outside.
Standard RMP = -70mV
Inside the cell is more negative than outside
What are ion channels?
They are permeable pores in the membrane which are selective for different ions, making the membrane selectively permeable.
Ion channels open/ close depending on transmembrane voltage, presence of activating ligands or mechanical forces (conformational changes)- i.e. you can either have voltage dependent or independent channels. You can get some channels that are always open.
Movement across the membrane will occur down the concentration gradient.
What is electrochemical equilibrium?
When the concentration gradient balances with the electrical gradient
What is equilibrium potential?
The potential at which electrochemical equilibrium has been reached. It is the potential that prevents diffusion of the ion down its concentration gradient.
Describe what is happening here
Case 1- you have equal conc of NaCl and KCl. There are no channels in the membrane so there is no diffusion. The membrane potential is 0mV
Case 3- The membrane has Na+ ion channels. Therefore there is movement of Na+ down its conc gradient from compartment 1 to compartment 2 (this is the direction of flux). 2 gets increasingly positive and 1 is more negative. The positive charge accumulates so the incoming Na+ will start to repel a little and there is reduced movement. Furthermore with the increasing charge differnece ( compartment 1 being so negative), some positive Na will be pulled back. When this settles, an electrochemical equilibrium is established- electrical forces balance out the diffusion forces.
The same stands if there were K+ channels in the membrane instead.
What is the nerst equation?
The nerst equation is a way of predicting the equilibrium potential for a given ion. Remember that the equilibrium potential is the potential that prevents diffusion down the ions conc gradient.
X is the concentration of the particular ion inside and outside the cell.
What establishes the resting membrane potential?
Due to diffusion of ions through selectively permeable membrane
Potassium is the main ions which controls resting membrane potential- the size of each ion’s contribution to membrane potential is proportional to the permeability of the membrane to that ion.
Equilibrium potentials of potassium and sodium
Real membrane potentials (-70mV) do not rest at the membrane potentials for neither sodium nor potassium.
This is because membranes have mixed K+ and Na+ permeability, but at rest, K+ >> Na+
The size of each ion’s contribution to membrane potential is proportional to the permeability of the membrane to that ion.
What is the goldman-hodgkin-katz (GHK) equation|?
It is a derivation of the nerst equation which takes into account the membrane permeability. Na, K, Cl concentrations all contribute to the real membrane potential. The size of each ion’s contribution is proportional to how permeable the membrane is to the ion.
Permeability is the probability the channel is open or closed: If P=1, 100% open, if P=0, 100% closed, if P=0.5, open 50% of the time.
GHK worked examples (this is not a question)
Beware of which concentration you are plugging in- i.e. if its the outside one or inside one.
What is membrane potential mainly governed by?
Potassium
What are the main stages (terminology) in the changes of membrane potential?
Depolarisation- change in the positive direction
Overshoot- change from 0 in the positive direction
Repolarising- change in the negative direction towards the resting direction
Hyperpolarisation- change in the negative direction beyond the resting potential
What is the difference between graded potentials and action potentials?
graded potentials are changes in the membrane potential in response to stimulation. There are changes in amplitude
Action potentials are an all or nothing event, they have uniform amplitude though.
What are graded potentials- what are their characteristics?
It is a stimulus, but not enough to cause depolarisation and firing of AP.
Graded potential changes, depending on the stimulus can be bi-directional (positive or negative).
Weak stimulus, small potential (small change in amplitude)
Strong stimulus, larger potential (greater change in amplitude)
With graded potentials, their amplitude will decrease over time and with distance from its point of origin.
Why does the amplitude decrease for graded potentials as the distance from the origin gets greater?
The movement of charge across the axon will slowly leak over time resulting in a decrease in the size of the graded potential.
Where do graded potentials occur? And what’s the point of them?
At synapses and sensory receptors
They contribute to initiating or preventing action potentials
Where do action potentials occur?
In excitable cells
Mainly in neurones and muscle cells
Also in some endocrine cells
True/ false:
Changes in the membrane potential during APs are due to ion pumps
FALSE
It is due to the movement of potassium
Why do we have action potentials?
In the neurones, they are known as nerve impulses and allow the transmissionof information reliably and quickly over long distances.
They play a huge role in cell-cell communication and can be used to activate intracellular contraction.
What does the permeability of a cell depend on?
The conformational state of the ion channels
They are:
Opened by membrane depolarisation
Inactivated by sustained depolarisation
Closed by membrane hyperpolarisation
When membrane permeability of an ion increases it crosses the membrane in a direction dictated by its electrochemical gradient. This movement changes the membrane potential toward the equilibrium potential for that ion.
AP- phase 1
Axon potentials are generated at the axon hillock
The membrane is more permeable to potassium than sodium (cheeky leaky potassium), this is why the RMP is closer to the equilibrium potential of potassium… so:
Pk >> PNa
At rest, the voltage gated channels are closed
AP- phase 2
Depolarising stimulus
The stimulus depolarises the membrane potential (becomes more +)
VGSC opens and Na enters the cell.
The stimulus needs to be above a certain threshold to generate an AP
AP- phase 3
Upstroke, depolarising phase
Starts at the threshold potential.
PNa is much greater because the VGSC opens much quicker than VGKC. Na+ channels enter down their electrochemical gradient.
PK is increasing too as the VGKC opens eventually. K+ leave the cell down their electrochemcial gradient. At there’s less Na+ entering the cell.
Membrane potential moves toward the Na+ equilibrium potential
AP- phase 4
Repolarisation
PNa reduces because the VGSC are inactivated- Na+ entry stops
More VGKC opens so PK increases and K+ continues to leave the cell down the gradient.
Membrane potential moves back towards the K+ equilibrium potential (in the negative area)
What is the absolute refractory period?
When the VGSC is inactivated and the VGKC is still open.
The inactive gate is shut and you cannot generate another AP in this state, even if there was a strong.
As it returns towards the RMP, the VGSC channel begins to close
AP-phase 5
Hyperpolarisation (and after)
VGKCs remain open for a while after repolarisation. K+ still leaves the cell down their electrochemical gradient.
Once equilibrium is established, the VGKC closes.
Membrane potential returns to RPM.
During after hyperpolarisation, sodium channel is closed and the inactivation gate is open.
What happens after hyperpolarisation?
Relative refractory period
The inactivation gate on the VGSC is open. It is opened by a chanage in the membrane potential, but because the membrane potential is already more negative, more stimulus is needed for the threshold. A stronger than normal stimulus is required to trigger an action potential.
what is the time course for changes in permeability?
Potassium channel open and close much slower than VGSC
The whole event is 2ms
Describe the regenerative relationship between the membrane permeability to sodium and membrane potential
Once the threshold potential is reached, an AP is triggered.
The cycle stops when the VGSC are inactivated due to the ball-chain mechanism. Inactivation means that they are closed and are voltage insensitive.
The membrane remains in an unresponsive state until the VGSCs recover from inactivation.
Stages of the regenerative relationship between PNa and membrane potential
- Once threshold is reached the cycle continues and positive feedback behaviour
- Cycle continues until VGSC are inactivated closed and voltage insensitive
- Membrane remains refractory stae until VGSC recover from inactivation.
Ion movement during the AP
Na enters and K leaves
A small number of ions cross the membrane and change the membrane potential- small conc change
ION PUMPS ARE NOT DIRECTLY INVOLVED IN ION MOVEMENT DURING AP
The electrochemical equilibrium is restored following AP by Na/K pumps
What affects the speed of an AP?
Diameter of axon and myelination.
What is passive propagation?
Only resting K+ channels open (cheeky leaky)
internal (or axial) and membrane resistance alters propagation distance and velocity
What is active propagation?
A local current will depolarise the adjacent area. If this is sufficient for depolarisation, then it will carry on. Cannot go into the cell body because it is in the absolute refractory period, not able to travel backwards. Can travel up to 120m/s
N.B myelination prevents loss of charge= insulator- allows the charge to travel further that with cable transport.
What affects conduction velocity?
It increase with axon diameter
Higher in myelinated axons
You can reduce it by reducing axon diameter, reducing myelination and with the cold, anoxia (lack of O2), compression and some drugs (anaesthetics)
