Membrane Potentials

Question 1

Define membrane potential

Answer 1

Membrane potential is the magnitude of an electrical charge that exists across a plasma membrane and is always expressed as the potential inside the cell relative to the extracellular solution. They are always measured in millivolts. (1x10-3V)

Question 2

What is the resting membrane potential of a:
Cardiac or skeletal muscle cell?
Nerve cell?
Erythrocyte?

Answer 2

Cardiac and skeletal muscle: -80 to -95 mV
Nerve cells: -50 to -75 mV
Erythrocyte: -5 to -9 mV (by far the smallest)

Question 3

What is the purpose of cells having membrane potentials?

Answer 3

Membrane potentials provide the basis of signalling in all types of cells.

Question 4

How do you measure a membrane potential?

Answer 4

One electrode of a voltmeter is attached to a microelectrode (tiny needle) and the other is placed extracellularly.
The microelectrode is a fine , glass pipette who’s tip diameter is less that micrometer. It’s filled with KCl (a conducting solution) and can penetrate the cell membrane. Therefore, it penetrates the cell membrane and the resting potential is measured.

Question 5

What are the minimum essential features that must be present in a system before a membrane potential can be established?

Answer 5

• Asymmetric distribution of ions across the plasma membrane (ion conc gradient).
• Selective ion channels in the plasma membrane (K, Na and Cl are the most important channel types but, there are many other types such as Ca, H and aquaporins which important as well).

Question 6

What are Ion channels?

Answer 6

They are proteins that enable ions to cross cell membranes. They have an aqueous pore through which ions flow by diffusion in both directions but, down their electrochemical gradient.

Question 7

What properties do ion channels have?

Answer 7

• Selectivity: They are selective for one (or a few) ion species. Eg the chloride ion channels would also let fluoride and bromide ions in,
• Gating: The pore can open or close by a conformational change in the protein. (They can also open slightly as well as just being open or closed),
• Rapid ion flow: ALWAYS down the electrochemical gradient.

Question 8

What is the extracellular concentration of potassium?

Answer 8

4.5mM

Question 9

What things decide what ions the membrane is permeable to? And how much by?

Answer 9

• how many channels are present

- Type of channels present (what ions and how much they are permeable)

Question 10

What would happen if you tried to set up a resting potential between two solutions but the membrane was totally permeable?

Answer 10

The two solutions (originally of different concentrations) would mix freely and they would become equal. There would be no charge on the membrane but, there would be moment of ions.

Question 11

What happens if you set up a resting potential between two solutions and the membrane is selectively permeable?

Answer 11

Eg if two solutions of KCl of varying conc were separated by a membrane that was only permeable to potassium ions, it would lead to a charge separation and the generation of an electrical gradient. This is the basis of the resting membrane potential.

Question 12

When does the resting membrane potential remain constant?

Answer 12

When the chemical diffusion gradient (movement of K outwards) and the electrical gradient (movement of K inwards) are equal and opposite. This will result in no net movement of ions. But, there will be a negative charge across the membrane which is the resting membrane potential.

Question 13

What is the Nernst equation and what does it allow you to calculate?

Answer 13

E= 61/z x log( conc outside / conc inside) at 37°C

The Nernst equation allows you to calculate the membrane potential at which the selected ion will be in equilibrium, given the extracellular and intracellular concentrations.

If a membrane is selectively permeable to that one ion alone then this value will be the membrane potential. However, this is never the case.

Question 14

What would the resting membrane potential in a cell be if it contained:

• Just potassium?
• Potassium, Sodium and Calcium?
• Potassium, Sodium, Calcium and Chloride?

Answer 14

K+ : -95 mV
K+,Na+, Ca+ : - 70 mV (they move in so make it less negative)
K+, Na+, Ca+, Cl-: -95 mV (moves in as well but it is negative)

Question 15

What ion channels dominate the resting membrane permeability?

Answer 15

Open potassium channels. This is because they have the largest difference intra and extracellularly

Question 16

What things can cause a change in membrane potential?

Answer 16

• Action potentials in nerve and muscle cells
• Triggering and control of muscle contraction
• Control of secretion of hormones and neurotransmitters
• Transduction of sensory information into electrical activity by receptors
• Postsynaptic actions of fast synaptic transmitters

Question 17

What is depolarisation?

Answer 17

A decrease in the size of the membrane potential from its normal value.
It causes the cell interior to become LESS NEGATIVE
Eg a change from -70mV to -50mV

Question 18

What is hyperpolarisation?

Answer 18

An increase in the size of the membrane potential from its normal value.
So the cell interior becomes MORE NEGATIVE.
Eg a change from -70mV to -90mV.

Question 19

What effect will increasing the membrane permeability for an ion have on the resting potential?

Answer 19

Increasing the membrane permeability for a particular ion moves the membrane potential towards the equilibrium potential for that ion.
So, changes in membrane potential are caused by changes in the activity of ion channels.

Question 20

What causes a change in membrane potential?

Answer 20

Changes in membrane potential are caused by change in the activity of ion channels.

Question 21

How do we deal with membranes that are not perfectly selective for one ion species?

Answer 21

The contribution of each ion to the membrane potential depends on the permeability of the membrane to that ion. The GHK equation is a that fits it fairly well (but isn’t perfect). It combines the Ernst equation for all the ions and the permeability factors.

Question 22

How do nicotinic acetylcholine receptors work?

Answer 22

They have an intrinsic ion channel that is opened by the binding of two molecules of acetylcholine. This channel will then let though Na+ and K+ (and all positively charged ions) but NOT anions. This will increase the membrane potential and move it closer to 0mV.

Many things such as nicotine, opiates, steroids and cannabis increase the activity of this receptor. This is why you get the shakes if you’re having withdrawal symptoms.

Question 23

What are the three different types of gating?

Answer 23

1. Ligand gating: This is when a channel opens or closes in response to the binding of a chemical ligand. Eg channel at synapses that respond to Ach or serotonin and channels that respond to intracellular messengers.
2. Voltage gating: This is when a channel opens and closes in response to changes in the membrane potential. Eg a channel involved in action potentials.
3. Mechanical gating: This is when a channel opens or closes in response to membrane deformation. Eg channels in mechanoreceptors, carotid sinus stretch receptors, hair cells in the inner ear ect…

Question 24

How do hair cells in the ear respond to mechanical gating?

Answer 24

1. Potassium channels close in the cuticular plate
2. This causes the membrane to depolarise
3. Depolarisation causes the calcium ion channels to open.
4. The calcium ions cause vesicles containing neurotransmitter (dopamine or dynorphin) to fuse with the basement membrane close to the afferent nerve.
5. Neurotransmitter diffuses across the synapse and binds with a receptor on the post synaptic plate. This generates an action potential down the efferent nerve that goes to the CNS for interpretation.

Question 25

What is fast synaptic transmission?

Answer 25

In fats synaptic transmission, the receptor protein is also the ion channel. Therefore, transmitter binding causes the channel to open.

Question 26

What are excitatory synapses?

Answer 26

Excitatory transmitters ops ligand gated channels that cause membrane depolarisation. They can be permeable to Na+, Ca+ and sometimes cations in general.
The resulting change in membrane potential is called an “excitatory post-synaptic potential” (EPSP)
This is:
-Longer than an action potential (20mS rather than 5mS)
-Graded with the amount of neurotransmitter
-Transmitters inc: Ach, Glutamate, Dopamine.

Question 27

What are inhibitory synapses?

Answer 27

Inhibitory transmitters open ligand-gated channels that cause hyperpolarisation. They are permeable to K+ and Cl-. The neurotransmitters used inc Glycine and GABA.

Question 28

What are the two basic patterns if slow synaptic transmission?

Answer 28

Slow synaptic transmission is when the receptor and the channel are two separate proteins.

1. Direct G-Protein gating. This is localised and therefore it is faster than the second pattern.
   Eg the receptor can bind to the G protein which then open a channel. (See other lectures for more depth)
2. Gating via an intracellular messenger. This signal is send throughout the cell (so the receptor and channel could be on opposite sides) this makes it slower than the first method. But, the signal is amplified via a cascade.
   Eg receptor binds to a G-protein which activates an enzyme (eg Adenyl Cyclase). This will the cause a signalling cascade (eg Protein Kinase A) which will activate either protein kinase (as mentioned) or an intracellular messenger. This will then cause the channel to open.

Question 29

What two other factors can influence membrane potential?

Answer 29

1. Changes in ion concentration
   The most important is the extracellular K+ concentration which is normally around 4mM. This is sometimes altered in clinical situations and it can alter the membrane excitability eg in the heart. Eg hyperkalemia is common in end stage renal failure and can cause cardiac arrest.
2. Electrogenic Pumps
   NaK-ATPase -All cells have one of these pumps. This moves three Na out for every two K in. However, this pump does not influence the membrane potential much only about -5mV so it makes the membrane potential more negative. This is the only pump present in erythrocytes.

Indirectly, the active transport of ions is responsible for the entire membrane potential because it sets up and maintains the ionic gradients that generate the resting membrane potential.