Cell signalling 2: electrical signalling (Prof. Patel)

Question 1

What is the membrane potential ?

Answer 1

The difference in voltage between the interior and exterior of the cell (~-70mV at rest).

Question 2

What are the concentrations of the main ions inside and outside the typical mammalian cell (in mM or pH units for H+) ?

Answer 2

Na+: intra = 5-15mM, extra = 145mM
K+: intra = 140mM, extra = 5mM
Mg2+: intra = 0.5mM, extra = 1-2mM
Ca2+: intra = 10E-4mM, extra = 1-2mM
H+: intra = pH = 7.2, extra = pH = 7.4
Cl-: intra = 5-15mM, extra = 110mM

Question 3

Why does the membrane potential arise ?

Answer 3

It arises due to ion gradients.

Question 4

What is the Nernst equation ?

What does it allow us to calculate ?

Answer 4

Nernst eq: V = (RT/zF) * ln(Co/Ci)

It allows calculation of the equilibrium potential for a given ion.

Question 5

What is the equilibrium potential for K+ ?

For Na+ ?

Answer 5

V(K+) = -90mV
V(Na+) = +60mV

Question 6

If the membrane potential comprises charge imbalance of all permeable ions, why is the resting potential closer to the equilibrium potential of K+ than any other ion ?

Answer 6

Because most cells are more permeable to K+ than other ions (“leak channels”).

Question 7

How can we calculate the value of the RMP ?

Answer 7

W/ the GHK equations.

Question 8

Is the membrane more permeable to K+, Na+ or Cl- ?

How does this permeability switch during the depolarization of a neural membrane (rising phase of the AP) ?

Answer 8

At rest: pK+&raquo_space; pCl-&raquo_space; pNa+

Active: pNa+&raquo_space; pK+&raquo_space; pCl-

Question 9

Why does the membrane potential not reach the Na+ equilibrium potential (+60mV) at its peak ?

Answer 9

Because of the fast inactivation of the Na+ channels.

Question 10

Which channels repolarize the neural membrane during the AP ?

Answer 10

V-gated K+ channels.

Question 11

Which channels mediate NT release ?

Answer 11

V-gated Ca2+ channels.

Question 12

What are the characteristics of the ionotropic Glu receptor ?

Answer 12

• extracellular N- terminus and intracellular C- terminus
• 4 trans-membrane regions (TMI to TMIV)
• inverted pore topology (structure of pore inverted compared to v-gated ion channels)
• 4 sub-units = 1 channel protein
• permeable to Na+/Ca+
• found at excitatory synapses

Question 13

What are the characteristics of the GABA-A receptor ?

Answer 13

• extracellular N- terminus and intracellular C- terminus
• Cys-loop receptor –> 2 loops linked by a disulfide bridge (2 cysteine residues)
• 4 transmembrane regions (M1 to M4)
• 5 subunits
• permeable to Cl- ions
• found at inhibitory synapses

Question 14

What are the characteristics of the nAChR ?

Answer 14

• Cys-loop receptor
• 4 transmembrane regions (M1 to M4)
• 5 subunits
• permeable to Na+
• found at excitatory synapses + NMJ
• 2 ACh molecules must bind for the channel to open

Question 15

How does ACh release lead to muscle contraction ?

Answer 15

nAChRs lets Na+ rush in the muscle cell + opens other v-gated Na+ channels, causing an end plate potential which might lead to a muscle AP.
This muscle AP depolarizes the T-tubules and opens Ca2+ channels of the SR, leading to a rise in sarcoplasmic [Ca2+] –> contraction