L6: Ion channels

Question 1

3 Main groups of ion channel

Answer 1

• Voltage-gated
• Neurotransmitter-gated
• Second messenger-gated

Question 2

Action potential brief overview

Answer 2

1) Na+ channels open - sodium influx, depolarisation
2) K+ channels open - potassium efflux, hyperpolarisation
3) Ca2+ channels open - calcium influx - resting potential
(transient depolarisation)

Question 3

4 examples of neurotransmitter-gated channels

Answer 3

AP response…
- Acetyl choline (selective for cations)
- Glutamate (selective for cations)
Inhibiting AP…
- Gamma-aminobutyric acid /GABA (selective for Cl-)
- Glycine (selective for Cl-)

Question 4

CNGCs (type of second messenger gated channel)

Answer 4

Type of 2nd-messenger-gated channel (Cyclic nucleotide-gated channels). Cation-selective and gated by cAMP or CGMP
- Retinal
- Olfactory

Question 5

IP3 receptors

Answer 5

• Type of 2nd messenger-gated channel (Inositol 1,4,5 triphosphate receptor)
• Ca2+ selective, release Ca2+ from ER to elevate cytosolic Ca2+ during cell signalling events

Question 6

Basic unifying structure of voltage-gated channels

Answer 6

• 6 Transmembrane spanning domain (S1-6)
• 1 pore (P) domain (pore-forming/selectivity filter)
• Voltage sensor (S4-TMS) - composed of positively charged AA residues
• Long N terminus which forms ‘ball and chain’ arrangement involved in inactivation (can swing round and block)
• Channels have 4 of these units - a tetramer in the case of K+, and a larger monomer in Na+, Ca2+

Question 7

Deactivation vs inactivation

Answer 7

• Deactivation: gate not open, voltage dependent
• Inactivation: gate open but pore blocked

Question 8

S.lividans K+ channel structure

Answer 8

Tetrameric channel with inverted ‘teepee’ structure

Question 9

Mechanism for ion selectivity in K+ channels

Answer 9

• K+ hydration shell less closely bound to the ion; must remove water to fit in channel, energy compensated for by that of binding to channel
• In Na+, however, hydration shell is much more tightly bound (smaller ion w/ higher charge density) - water removal can’t be compensated so remains hydrated, can’t fit through channel

Question 10

How do bound K+ ions move through the channel?

Answer 10

• Tight binding, selective for K+
• Binding sites at defined stages along channel
• Electrical repulsion of incoming K+ pushes next ion further along

Question 11

Sodium channel selectivity

Answer 11

• Wider channel than K+; partially dehydrated ions enter channel

Question 12

Role of S4

Answer 12

• Involved in voltage sensing
• Positive charges distributed as a helix around channel
• Sliding helix model (changes in voltage force the Arg residues to move up through membrane, forces conformational change which opens gate)