M&R Session 3: resting cell membrane

Question 1

What is the resting cell membrane potential an expression of?

Answer 1

Voltage inside relative to voltake outside the cell

Question 2

How is the resting membrane potential formed?

Answer 2

Unequal distribution of one or more ion species across membrane
and
Membrane is permeable to one or more of these species (by ion channels that are selective, gated and ions flow down the electrochemical gradient)

Question 3

How is the membrane potential measured?

Answer 3

Microelectrode filled with a conducting solution (potassium chloride)
Penetrates membrane
Records potential relative to inside face with respect to the outside

Question 4

What is the resting membrane potential?

Answer 4

The membrane potential when the cell is not excited
An equilibrium where the driving force for membrane-permeable ions down conc. gradients is equal and opposite to the driving forces for these ions

Question 5

Range of resting membrane potentials for animal cells?

Answer 5

-20 to -90 mV

Question 6

Resting membrane potential for cardiac and skeletal muscle?

Answer 6

-80 to -90 mV

Question 7

Resting MP for neurones?

Answer 7

-50 to -75 mV

Typically -70 mV is used

Question 8

Describe how the resting membrane potential is established

Answer 8

1. Open K+ channels, [K+]in

Question 9

Why is the resting MP set predominantly by K+ ions?

Answer 9

Because more K+ channels are open than Na+/Ca2+ channels

Question 10

What is the Nernst equation?

Answer 10

Calculates equilibrium potential for an ion

Eion= 61/z (log [ion]o/[ion]i)
z= valency, e.g. Na+ valency=+1

Question 11

What is the effect of increasing [K+]o on the resting potential?

Answer 11

Makes Ek more positive

So MP is more positive

Question 12

What is the role of Na+-K+-ATPase in the resting MP?

Answer 12

Minimal role: contributes ~-5mV

Provides the outward concentration gradient for K+, as actively moves Na+ and K+ against their concentration gradients

Question 13

How might changing the membrane potential be used for cell signalling?

Answer 13

Nerve and muscle cell action potentials
Control of neurotransmitter and hormone secretion
Postsynaptic actions of fast synaptic transmitters
Triggering and control of contraction
Transduction of sensory information into electrical activity by receptors

Question 14

Define depolarisation

Answer 14

Membrane potential becomes more positive

Question 15

Define hyperpolarisation

Answer 15

Membrane potential becomes more negative than normal

Question 16

How do ion channels contribute to changes in the membrane potential?

Answer 16

Increasing permeabilty to an ion moves the membrane potential towards Eion
Opening of Na+ or Ca2+ channels depolarises
Opening of K+ or (usually) Cl- channels hyperpolarises

Question 17

State the equilibrium potentials for K+, Na+, Cl- and Ca2+

Answer 17

K+: -90mV
Na+: +60 mV
Cl-: -65 mV
Ca2+: +135 mV

Question 18

What is the use of the Goldman-Hodgkin-Katz equation?

Answer 18

Approximates the contribution of each ion to the membrane potential in order to decide how permeable the membrane is to that ion: as real cell membranes aren’t perfectly selective

Question 19

Describe the 3 methods of channel gating

Answer 19

1. Ligand gating: channel opens or closes due to binding of a chemical ligand. E.g. channels at synapses that respond to neurotransmitters
2. Voltage gating: channel opens or closes due to changes in MP. E.g. VOCCs
3. Mechanical gating: channel opens or closes due to membrane deformation. E.g. carotid sinus stretch receptors

Question 20

Describe slow synaptic transmission

Answer 20

Receptor and channel are separate proteins
Gating can be either:
1. Direct G-protein gating: localised and fairly rapid
or
2. Gating via an intracellular messenger: generalised over the cell, amplification by cascade

Question 21

Describe fast synaptic transmission

Answer 21

Receptor protein is also an ion channel. Opens directly upon binding by its agonist
E.g. nAChR opens when ACh binds allowing Na+ influx
Excitatory or inhibitory synapses

Question 22

Excitatory synapses?

Answer 22

Type of fast transmission
Excitatory transmitters (e.g. ACh, glutamate) open ligand-gated channels, causing depolarisation
Can be permeable to Na+, Ca2+, cations
Change in MP called the EPSP: longer time course than an AP, graded with amount of neurotransmitter

Question 23

Inhibitory synapses?

Answer 23

Type of fast transmission
Inhibitory transmitters (e.g. glycine, GABA) open ligand-gated channels, causing hyperpolarisation
Permeable to K+ or Cl-

Question 24

What are the ionic causes and consequences of hyperkalaemia?

Answer 24

Excess extracellular K+, so more positive resting MP, so less change in conductance for depolarisation
Therefore, cardiac membrane excitability increases and ventricular arrhythmias result
Can also prevent the repriming of inactivated Na+ channels causing an electrically “silent” membrane