Membrane Potential

Question 1

What is the membrane potential of a cell?

Answer 1

The magnitude of an electrical charge (mV) that exists across a plasma membrane.
Negative at rest in all mammalian cells.

Question 2

Give examples of resting cell membrane potentials.

Answer 2

• Cardiac and skeletal muscle cells have largest resting potentials: -80mV to -95 mV.
• Nerve cells: -50mV to -75mV.
• Erythrocytes have the smallest: -9mV.

Question 3

How is MP measured?

Answer 3

Using a voltmeter and microelectrode.

Question 4

What are the 2 minimum essential factors in generation of the MP?

Answer 4

• Asymmetric distribution of ions across the PM (i.e. Ion conc gradients)
• Selective ion channels in the PM: K+, Na+ and Cl- channels are the most important for most cells

Question 5

Describe the selective permeability of the plasma membrane.

Answer 5

Phospholipid bilayer has a hydrophobic interior so

• is permeable to small uncharged molecules (O2, CO2, H2O, benzene)
• but very impermeable to charged molecules (ions) - requires ion channels

Question 6

What are the properties of ion channels?

Answer 6

Have an aqueous pore through which ions flow by diffusion in both directions down their chemical gradient.

1. Selectivity: for one (or a few) ions species
2. Gating: pore can open or close by a conformational change in the protein
3. Rapid ion flow (microsecs)

Question 7

Describe the ionic concentrations for a typical mammalian cell.

Answer 7

Intracellular Extracellular (plasma)

Na+ 10mM. Na+ 145mM
K+ 160mM. K+ 4.5mM
Cl- 3mM. Cl- 114mM
A- 167mV. A- 40mM

Question 8

What dominates the membrane inonic permeability at rest?

Answer 8

• Open K+ channels
• When the K+ chemical gradient and electrical gradient are equal and opposite, there will be no net movement of K+ but there will be a negative charge across the membrane - the resting MP.
• So resting MP arises due to selective permeability to K+.

Question 9

What does the Nernst equation calculate?

Answer 9

• The MP at which an ion will be in equilibrium, given the extracellular and intracellular concentrations of the ion.
• E.g. Ek = K+ equilibrium potential = -95mV

Question 10

What are depolarisation and hyperpolarisation?

Answer 10

• Depolarisation: decrease in the size of the MP from its normal value - cell interior becomes less negative.
• Hyperpolarisation: increase in the size of the MP from its normal value - cell interior become more negative.

Question 11

What causes changes in MP?

Answer 11

• Changes in the activity of ion channels - move the MP towards the equilibrium potential of those ions.

Question 12

In which cells do K+ channels have an important effect on MP?

Answer 12

• Cardiac muscle cells (-80mV) and nerve cells (-70mV): resting MP quite close to Ek but not exactly as membrane not perfectly selective for K+.
• Skeletal muscle: many Cl- and K+ channels open in resting membrane so resting potential = 90mV, close to both Ek and Ecl.
• Cells with lower resting MPs have lower selectivity for K+ - increased contribution from other channels. E.g. Smooth muscle cells (-50mV), erythrocytes have virtually no K+ selectivity (-9mV).

Question 13

Opening of which channels leads to hyperpolarisation and depolarisation?

Answer 13

• Opening Na+ or Ca2+ channels - depolarisation (Ena = +70mV, Eca = +122 mV).
• Opening K+ or Cl- channels - hyperpolarisation (Ek = -95mV, Ecl = -96mV).

Question 14

What is membrane conductance?

Answer 14

How permeable a membrane is to specific ions (i.e. The number of open channels for that ion).

Question 15

Which equation describes the imperfect selectivity of membranes?

Answer 15

Goldman-Hodgkin-Katz equation (involves relative permeabilities to K+, Na+ and Cl-).

Question 16

How can channel activity be controlled?

Answer 16

• They are gated:
  1. Ligand gating - open/close in response to binding of a chemical ligand.
  2. Voltage gating - open/close in response to changes in MP.
  3. Mechanical gating - open/close in response to membrane deformation (e.g. Hair cells of the inner ear).

Question 17

What do ligand-gated channels give rise to?

Answer 17

Synaptic potentials

Question 18

Where do synaptic connections occur?

Answer 18

Between:

• nerve cell - nerve cell
• nerve cell - muscle cell
• nerve cell - gland cell
• sensory cell - nerve cell

Question 19

What is the difference between fast and slow synaptic transmission?

Answer 19

• Fast (microseconds): the receptor protein is also an ion channel - transmitter binding causes channel to open.
• Slow (milliseconds): the receptor and channel are separate proteins.

Question 20

Describe fast synaptic transmission at excitatory synapses.

Answer 20

• Excitatory transmitters (e.g. ACh, glutamate, dopamine) open ligand-gated ions channels that cause membrane depolarisation (excitatory post-synaptic potential).
• Channel can be permeable to Na+, Ca2+ or sometimes cations in general (e.g. nAChR).
• Longer time course than an AP (1/2 msec) and graded by transmitter amount).

Question 21

How are the actions of inhibitory transmitters different to those of excitatory transmitters at synapses?

Answer 21

Inhibitory transmitters (e.g. Glycine, GABA) open ligand-gated channels that cause hyperpolarisation - more permeable to K+ or Cl-.

Question 22

What is summation?

Answer 22

Process that determines whether an AP will be triggered by the combined effects of excitatory and inhibitory signals from:

• multiple simultaneous inputs (spatial summation)
• repeated inputs (temporal summation)

Question 23

What are the 2 types of slow synaptic transmission?

Answer 23

1. Direct G-protein gating: localised and relatively rapid (as G-protein doesn’t move far to get to channel). Involves GTP to GDP hydrolysis.
2. Gating via an intracellular messenger: acts throughout the cell and can be amplified by an enzyme cascade. Requires more time as several intermediates, culminating in intracellular messenger or protein kinase activating channel.

Question 24

Which 2 additional factors can influence membrane potential?

Answer 24

1. Changes in ion concentration - sometimes altered in clinical situations, can alter membrane excitability, e.g. In heart. Most important is extracellular K+ concentration.
2. Electrogenic pumps (e.g. Na+/K+ ATPase) - in some cells, this contributes a few mV directly to MP, making it more negative (e.g. In erythrocytes).