Resting and action potential

Question 1

What is diffusion?

Answer 1

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.

Question 2

What is the electrical potential?

Answer 2

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

Question 3

What is flux?

Answer 3

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

Question 4

What are the properties of ions?

Answer 4

Ions= charged molecules. Like charges repel, opposite charges attract.

Question 5

What are the electrical properties of excitable cells?

Answer 5

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)

Question 6

What are the 2 gradients associated with movement across the cell membrane?

Answer 6

• Diffusion (concentration) gradient
• Charge gradient

Question 7

What is the convention in measuring resting membrane potential?

Answer 7

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

Question 8

What are ion channels?

Answer 8

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.

Question 9

What is electrochemical equilibrium?

Answer 9

When the concentration gradient balances with the electrical gradient

Question 10

What is equilibrium potential?

Answer 10

The potential at which electrochemical equilibrium has been reached. It is the potential that prevents diffusion of the ion down its concentration gradient.

Question 11

Describe what is happening here

Answer 11

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.

Question 12

What is the nerst equation?

Answer 12

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.

Question 13

What establishes the resting membrane potential?

Answer 13

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.

Question 14

Equilibrium potentials of potassium and sodium

Answer 14

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.

Question 15

What is the goldman-hodgkin-katz (GHK) equation|?

Answer 15

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.

Question 16

GHK worked examples (this is not a question)

Answer 16

Beware of which concentration you are plugging in- i.e. if its the outside one or inside one.

Question 17

What is membrane potential mainly governed by?

Answer 17

Potassium

Question 18

What are the main stages (terminology) in the changes of membrane potential?

Answer 18

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

Question 19

What is the difference between graded potentials and action potentials?

Answer 19

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.

Question 20

What are graded potentials- what are their characteristics?

Answer 20

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.

Question 21

Why does the amplitude decrease for graded potentials as the distance from the origin gets greater?

Answer 21

The movement of charge across the axon will slowly leak over time resulting in a decrease in the size of the graded potential.

Question 22

Where do graded potentials occur? And what’s the point of them?

Answer 22

At synapses and sensory receptors

They contribute to initiating or preventing action potentials

Question 23

Where do action potentials occur?

Answer 23

In excitable cells

Mainly in neurones and muscle cells

Also in some endocrine cells

Question 24

True/ false:

Changes in the membrane potential during APs are due to ion pumps

Answer 24

FALSE

It is due to the movement of potassium

Question 25

Why do we have action potentials?

Answer 25

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.

Question 26

What does the permeability of a cell depend on?

Answer 26

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.

Question 27

AP- phase 1

Answer 27

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: P_k \>\> P_Na At rest, the voltage gated channels are closed

Question 28

AP- phase 2

Answer 28

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

Question 29

AP- phase 3

Answer 29

Upstroke, depolarising phase Starts at the threshold potential. P_Na is much greater because the VGSC opens much quicker than VGKC. Na+ channels enter down their electrochemical gradient. P_K 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

Question 30

AP- phase 4

Answer 30

Repolarisation P_Na reduces because the VGSC are inactivated- Na+ entry stops More VGKC opens so P_K increases and K+ continues to leave the cell down the gradient. Membrane potential moves back towards the K+ equilibrium potential (in the negative area)

Question 31

What is the absolute refractory period?

Answer 31

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

Question 32

AP-phase 5

Answer 32

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.

Question 33

What happens after hyperpolarisation?

Answer 33

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.

Question 34

what is the time course for changes in permeability?

Answer 34

Potassium channel open and close much slower than VGSC The whole event is 2ms

Question 35

Describe the regenerative relationship between the membrane permeability to sodium and membrane potential

Answer 35

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.

Question 36

Stages of the regenerative relationship between P_Na and membrane potential

Answer 36

* 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.

Question 37

Ion movement during the AP

Answer 37

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

Question 38

What affects the speed of an AP?

Answer 38

Diameter of axon and myelination.

Question 39

What is passive propagation?

Answer 39

Only resting K+ channels open (cheeky leaky) internal (or axial) and membrane resistance alters propagation distance and velocity

Question 40

What is active propagation?

Answer 40

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.

Question 41

What affects conduction velocity?

Answer 41

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)