M&R 3.1/3.2 RMP & Changing Membrane Potential

Question 1

How can we measure the membrane potential?

Answer 1

Using a micropipette filled with conducting solution (KCl) to penetrate the cell membrane and measure the voltage inside the cell. The voltage inside the cell with respect to the voltage outside the cell is the membrane potential.

Question 2

What is the RMP in skeletal muscle?

Answer 2

Usually ~-90mV

Question 3

What is the RMP in a neuron?

Answer 3

Usually -70mV

Question 4

What is the RMP of a cardiac myocyte?

Answer 4

~-85mV

Question 5

What is the RMP of a sino-atrial node cell?

Answer 5

No true RMP because they are always gradually depolarising (pacemaker potential).
But ~-60mV when fully repolarised
Gradually depolarise to the threshold for the AP (between -30 and -40mV)

Question 6

What main factor is responsible for the RMP?

Answer 6

Open K+ ‘leak’ channels at rest

Question 7

Describe the how the RMP is set up

Answer 7

(Na+/K+ ATPase has already set up a concentration gradient so there is more K+ inside and more Na+ outside)
At rest membrane has open K+ ‘leak’ channels so is selectively permeable to K+
K+ diffuses out of the cell down its conc gradient, so cell becomes more negative inside
Therefore as K+ leaves down its conc gradient, it is creating an electrical gradient that pulls it back into the cell
When the chemical & electrical gradients for K+ are equal & opposite, there will be no net movements of K+
The remaining membrane potential is negative

Question 8

What is the equilibrium potential for K+ (Ek)

Answer 8

Ek = -95mV

Question 9

Why is the RMP close to, but not the same as, Ek?

Answer 9

Open K+ channels dominate the resting permeability, so RMP is close to Ek
But membrane not perfectly selective for K+ - other channels are open
Therefore RMP is slightly less negative than Ek

Question 10

What is depolarisation?

Answer 10

A decrease in the size of the MP from normal value
The inside of the cell becomes less negative with respect to the outside (e.g. -70mV -> -50mV) and therefore lies closer to threshold potential

Question 11

What is hyperpolarisation?

Answer 11

An increase in the size of the MP from normal value
The inside of the cell becomes more negative with respect to the outside (e.g. -70mV -> -90mV)
Therefore is further from the threshold potential so the cell is harder to depolarise

Question 12

What happens when membrane permeability to a particular ion is increased?

Answer 12

It moves the MP towards the equilibrium potential for that ion

Question 13

What is the equilibrium potential for chloride?

Answer 13

ECl- = -96mV

Question 14

What is the equilibrium potential for sodium?

Answer 14

ENa+ = +70mV

Question 15

What is the equilibrium potential for calcium?

Answer 15

ECa2+ = +122mV

Question 16

Increasing membrane permeability to K+ or Cl- causes _________

Answer 16

Hyperpolarisation

because they both have a negative equilibrium potential, so it makes the inside of the cell more negative

Question 17

Increasing membrane permeability to Na+ or Ca2+ causes ___________

Answer 17

Depolarisation

because they both have a positive equilibrium potential, so shift the MP closer to threshold

Question 18

The contribution of each ion to the MP depends on how permeable the membrane is to that ion. What does the permeability depend on?

Answer 18

1. The number of available channels

2. How easily the channels let the ion through

Question 19

Name 3 mechanisms by which membrane ion channel opening can be controlled

Answer 19

1. Ligand gating
2. Voltage gating
3. Mechanical gating (responds to membrane deformation due to stretch - e.g. carotid sinus stretch receptors)

Question 20

What is fast synaptic transmission?

Answer 20

The receptor protein is also a ligand-gated ion channel, so transmitter binding causes the channel to open.

Question 22

What happens during an EPSP (excitatory post-synaptic potential)

Answer 22

Excitatory transmitters open ligand-gated ion channels with positive reversal potentials (permeable to Na+/Ca2+ or cations in general)
Movement of these ions causes membrane depolarisation
This membrane depolarisation is called an EPSP

Question 23

Is an EPSP the same as an AP? Why?

Answer 23

No
1. An EPSP is a graded depolarisation of the MP, with gradual return to RMP.
An AP is a rapid depolarisation, followed by a brief hyperpolarisation and then repolarisation to RMP.

2. EPSPs are graded - the more excitatory transmitter, the larger the initial depolarisation and therefore the EPSP.
   APs are always the same size. The intensity of the stimulus is encoded by the frequency of the APs, not the size.
3. EPSPs can have an additive effect, so that lots of small EPSPs in a short space of time can add together to make the membrane reach threshold.
   APs are all-or-nothing. They only occur once the MP has reached a threshold potential. If threshold potential is not reached, there is no AP.

Question 24

Name 2 excitatory transmitters that could trigger an EPSP

Answer 24

Acetylcholine

Glutamate

Question 25

What happens during an IPSP (inhibitory post-synaptic potential)?

Answer 25

Inhibitory transmitters open ligand gated ion channels with negative reversal potentials (permeable to K+ or Cl-)
Movement of these ions causes membrane hyperpolarisation
This leads to inhibition - because MP is driven further from threshold potential, so it is harder to depolarise the cell

Question 26

EPSPs and IPSPs are examples of _____ synaptic transmission

Answer 26

Fast

transmitter binds to a ligand-gated ion channel and causes it to open

Question 27

What is slow synaptic transmission?

Answer 27

The receptor protein and the ion channel are two separate proteins.
Therefore some form of communication system is required so that the activated receptor can activate the ion channel.

Question 28

Name 2 methods of slow synaptic transmission. Briefly describe how they work, and 2 main features of each

Answer 28

1. Direct G-protein gating: The G protein on a GPCR laterally transfuses in the membrane to act on the ion channel.
   Localised
   Quite rapid
2. Gating via intracellular messengers : the G-protein binds to an enzyme which activates an intracellular signalling cascade. Products may directly bind to channel, or activate a protein kinase which can phosphorylate the channel.
   Pathways occur in cytoplasm so can activate channels far away
   Amplification by cascade (e.g. if an enzyme in the cascade produces thousands of products - the message is amplified)

Question 29

Aside from opening ion channels, name 2 other factors that can influence membrane potential

Answer 29

1. Changes in ion concentration (particularly extracellular K+ concentration)
2. Electrogenic pumps
   Na+/K+ ATPase moves 3Na+ out of cell and 2K+ in
   Not primarily responsible for RMP but contributes ~-5mV
   And sets up/maintains ionic gradients, so is indirectly responsible for the rest of the RMP (dissipation of the gradient through ion channels is what sets the RMP)

Question 30

What effect does hyperkalaemia have on membrane potential & excitability?

Answer 30

Hyperkalaemia = increased extracellular K+ conc

• > Reduces conc gradient between inside & outside of cell
• > therefore less outflow of K+ through leak channels
• > so RMP will be less negative (more depolarised) and closer to threshold
• > therefore cell more excitable

Question 31

Name to inhibitory transmitters that could trigger an IPSP

Answer 31

Glycine

GABA (gamma-aminobutyric acid)