ligand gated channels

Question 1

how do ions move through the ligand gated channels

Answer 1

Note ions loose their hydration shells to fit through filter, they move single file, with electrostatic repulsion propelling them through. Flow down electrochemical gradient

Question 2

Structure of a Voltage-gated K channel-Kv1 and what happens for it to open

Answer 2

• Structure of a Voltage-gated K channel-Kv1 is made up of 4 a subunits (each with 6 TMs) creating a pore in the center (defined by S5 and S6)

‘p loop’ providing selectivity filter (same as previous slide), but additional TMs labelled S1-S4 sense voltage.

Negative membrane potential sensed by S4, keeps gate closed, if membrane depolarizes S4 moves and gate opens.

S4 domain, pulls on S5 to open gate. Channels inactivate when ‘inactivating peptide’ swings into place blocking the pore.

cytoplasmic beta subunits also add extra regulatory components

Question 3

cyclic nucleotide gated channel structure

Answer 3

a tetramer, with similar domain organization of 6 TMs, with S5 & S6 alpha helical domains lining central pore with P loop controlling filter, but now we have added regulatory domains to the intracellular N and C terminals.

Question 4

cyclic nucleotide gated channel action

Answer 4

• Cyclic nucleotide binding domain on intracellular C terminal domain opens a pore permeable to Na+ and Ca+.
• Ligand must bind to 3 of the four sites for the channel to open, loose 1 and you close…gives a sharp ‘concentration’ response curve.
• Calcium binding to N’terminal associated calmodulin provides negative feedback.

Question 5

P2X channels structure and what causes it to open

Answer 5

• gated by binding of extracellular ATP.
• composed of just 2TMs, three of which come together in a ‘trimeric’ assembly to form the channel.
• ATP binds to pockets on the extracellular face of the channel.

Question 6

glutamate receptors structure

Answer 6

• tetrameric ligand gated ion channels

* Form as dimer of dimers, ligand binding site is in a cleft close to the plasma membrane that ‘closes’ when occupied

Question 7

what activate glutamate receptors and their action

Answer 7

Most glutamate receptors Are Na/K+ selective ion

ligand binding domain is in cleft near the pm.

Glutamate binding allows the cleft to ‘close’ like a clamshell producing tension on TM domains (M1, M2, M3) that pulls channel open.

Spontaneous rearrangements in extracellular domains cause channel to snap shut into ‘inactive desensitized state with ligand still bound

Question 8

nACHr in muscle (cysloop) structure and action

Answer 8

of 5 subunits Each has 4 TMs (M1,M2,M3,M4)

large external facing N domain and intracellular loops btween M3 and M2 line pore

Ach binds in pocket in the alpha subunit.

Binding of ACH cause M2 subunits to rotate opening a pore permeable to hydrated cations ions.

Question 9

CHRNA4 mutation in nACh R what is the pathology

Answer 9

causes epilepsy seizures