ICPP 7 - Resting + Changing Membrane Potential

Question 1

What is a “membrane potential”?

Answer 1

An electrical potential (voltage) difference across a cells plasma membrane.

Question 2

How would you measure a membrane potential?

Answer 2

• Apply a glass micro-electrode that penetrates a cell membrane
• Add conducting solution, e.g.: KCl
• Can see displacement in membrane potential on voltmeter (-75mV resting potential).

Question 3

What is the resting membrane potentials in:

1) Cardiac myocytes
2) Neurones
3) Skeletal muscle myocytes
4) Smooth muscle myocytes

Answer 3

1) -80mV
2) -70mV
3) -90mV
4) -50mV

Question 4

What is selective permeability of the cell membrane?
What confers this selectivity?
What are 3 properties of the proteins that confer this selectivity?

Answer 4

• Cell membrane is only permeable to certain molecules (small, uncharged, hydrophobic), very impermeable to ions.
• Ion channels allow certain ions to cross the cell membrane.
• Their 3 properties are 1) selectivity 2) gating 3) rapid ion flow.

Question 5

What is the typical EC and IC ion concentrations in a typical mammalian cell for Na, K, Cl and anions other than Cl-?

Answer 5

IC:
Na = 12nM
K = 140mM
Ca = 0.0001 mM
Cl- = 4.2mM
A- = 167mM

EC:
Na = 145mM
K = 4.5 mM
Ca = 2mM
Cl = 123mM
A = 40mM

Question 6

What sets up the resting membrane potential of -70/-75mV?

Why is the resting membrane potential not strictly Ek?

Answer 6

• The selective permeability of the membrane to K+ ions at rest.
• Ek (-95mV), however there is a small influx (leakage) of positive Na+ and Ca2+ ions through leakage channels at rest which provides some positive charge, so it slightly more positive than Ek at around -70/-75mV.

Question 7

How do you calculate the equilibrium potential for an ion across the membrane?

Answer 7

• The Nenst Equation (RT/zF Log (Ion(o)/Ion(i)))
• Can replace RT/zF for 61 in monovalent cations
• For Ca2+ change valency (z) to 2
• For anion change valency to negative (e.g.: -1 for Cl-)

Question 8

What is depolarisation and hyperpolarisation?

Answer 8

Depolarisation = cell becoming less negative
Hyperpolarisation = cell becoming more negative

Question 9

How does depolarisation + hyperpolarisation of the membrane occur?
Which channels are responsible for each?

Answer 9

• Changes in selective permeability of ion channels, as the permeability for the channel increases, mV moves towards the Ek for that ion.
• K+ and Cl- = Hyperpolarisation
• Na+ and Ca2+ = Depolarisation

Question 10

How is the membrane potential of membranes permeable to multiple ions worked out?

Answer 10

Via the GHK equation - takes into account permeability of membrane to each individual ion.

Question 11

Name an ion channel that is less selective to particular ions

Answer 11

NAChR - at neuromuscular junction, ACh binds, causing opening of integral ion channel that is permeable to cations such as Na+ and Ca2+

Question 12

What are the 3 types of gating a channel could possible have?

Answer 12

1) Ligand-Gated - channel opens in response to ligand, e.g.: channels at synapses
2) Voltage-gated - Channels open in response to changes in mV, e.g..: VG Na+ channels
3) Mechanical-Gating - change in response to membrane deformation, e.g.: hair cells

Question 13

How does fast synaptic transmission work?

Answer 13

The receptor is also an ion channel, binding of transmitter opens integral ion channel, e.g.: NAChR

Question 14

What is the difference between excitatory and inhibitor synapses? Give examples of excitatory and inhibitory transmitters.

Answer 14

• Excitatory synpases open ligand-gated ion channels that DP the membrane, resulting in EPSP’s that may summate to generate an AP. Transmitters = glutamate, + ACh
• Inhibitory synapses open ligand-gated ion channels that HP the membrane and generate IPSP’s - transmitters = glycine + GABA

Question 15

What are the 2 types of slow synaptic transmission

Answer 15

1) Direct G-protein gating - G-protein activated and transduces signal to open ion channel
2) Gating via IC messenger - G-protein activates signalling cascade that results in IC messenger activating ion channel.

Question 16

What 2 other factors may influence membrane potential?

Answer 16

1) Changes in ion concentration - most importantly K+ ions, in hyperkalaemia membrane excitability in heart is increased, leads to inappropriate AP’s and arrhythmias
2) Electrogenic pumps - e.g.: Na/K ATPase, generates a small negative contribution to resting membrane potential (-5/-10mV), however largest role is maintaining concentration gradients for Na and K in resting membrane potential.