Ligand-Gated Ion Channels

Question 1

Agonists & Antagonists

Answer 1

Full agonist: Binds & activates with maximum response
Partial agonist: Bind & activate with partial efficacy event at max. Receptor occupancy
Superagonist: Greater response than a full agonist
Inverse agonist: Same binding as agonist but inhibits activtiy → Can bring down the baseline activity of the channel
Antagonist: Blocks channel response

Question 2

Structure of glutamate receptors

Answer 2

COOH domain for opening necessary
Large ec amino terminal domain & Ec ligand binding domain
Transmembrane domain (3 alpha-helices (M1, M3, M4) & loop M2 between M1 & M3

Question 3

AMPA

Answer 3

Tetramer (GluA1, A2, A3, A4) → Conducts Na+ & K+ (Normally also Ca2+ but through RNA editing (arginine) in GluA2 no more conduction of Ca2+)
Co receptors: TAPPy2 & PSD-95 → Membrane localization & post synaptic densitiy

Question 4

NMDA

Answer 4

Heterotetramers (2x GluN1 & 2 x GluN2)
Conductance for Na+, K+ & Ca2+
Additional binding site for co-factors → Mg2+ binding = Blockage of pore
Activation: Repetitive stimulation → More glutamate activates MPA → Increase of ic Na+ → Increase of postsynaptic potential & depolarization → Release of Mg2+ → Opening

Question 5

Role of NMDA in Alzheimers

Answer 5

Blockage of EEAT by Beta-Amyloid → Glutamate excess in synaptic cleft → Increased activity of NMDA → Increased Ca2+ in postynapse → pTau & Cell death

Question 6

Glycine Receptors

Answer 6

Inhibitory → Passing of Cl- (Cys-Loop-Receptor)
Structure of Cys-Loop receptors: Large ec amino-terminal domain & Transmembrane domain (5 alpha helices, M2 = Pore)
Defect: Startled responses → Fainted goat disease, Hypoplexia

Question 7

GABA-A

Answer 7

Cys-loop receptor (Subunits encoded on different chromosomes) → Pentamer, 2 GABA binding sites → Selectively permable for Cl-

(GABAC also ionotropic)

Question 8

Nicotinic Acetylcholine Receptors (nAChR)

Answer 8

Cys-Loop-Receptor → 5 subunits
Conducts Na & K+
Important at the muscular end-plate