Ligand-Gated Ion Channels

Question 1

What is a receptor superfamily?

Answer 1

A group of receptors with a similar basic molecular structure and that use the same signal transduction pathway

Question 2

List the major receptor superfamilies

Answer 2

• LGICs
• GPCRs
• Kinase-linked receptors
• Nuclear receptors (extracellular)

Question 3

What is a LGIC?

Answer 3

Diverse superfamily of multimeric integral membrane proteins that incorporate extracellular ligand- binding sites & a central transmembrane ion-permeable channel/pore

Question 4

When an ion flows through the activated channel what happens?

Answer 4

Modulation of cellular function

Question 5

LGICs involved in a wide range of biological functions, give examples

Answer 5

• Synaptic transmission & neural communication
• Cell excitation
• Muscle contraction & intracellular signalling

Question 6

(Excitatory) Mediate influx of cations causes membrane ____

Answer 6

depolarisation

Question 7

(Inhibitory) Mediate influx of anions causes membrane ____

Answer 7

hyperpolarisation

Question 8

List the receptor classification of LGIC based on mol structure & subunit stoichiometry

Answer 8

• Cys-loop receptor family (pentameric - 5 subunits) e.g. nAChR
• Ionotropic glutamate receptor family (tetrameric - 4 subunits)
• P2X receptor family (trimeric - 3 subunits)

Question 9

Cys-loop receptors arranged around a _______ _________

Answer 9

central ion conducting pore

Question 10

Ionotropic are _______

Answer 10

non-selective cation channels gated by glutamate

Question 11

P2X are ________

Answer 11

non-selective cation channels gated by extracellular ATP

Question 12

Cys-loop LGIC activated by neurotransmitter _____ and also by ____

Answer 12

acetylcholine

nicotine, hence AChR

Question 13

Binding of ACh, influx of ____ then membrane depolarisation, influx of ____ & neurotransmitter release

Answer 13

Na + ions

Ca 2+

Question 14

List the nicotine acetylcholine receptors

Answer 14

• Muscle (Nm) subtype (occur at NMJ)

- Neuronal (Nn) subtype (occur at autonomic ganglia in CNS)

Question 15

Where are the 2 ACh binding sites

Answer 15

• At the interface between the two a subunits and neighbouring y/e subunits

Question 16

Autonomic nervous system

• Nm mediates fast excitatory synaptic transmission >
• Nn mediates same & autonomic control of peripheral organs

Answer 16

• skeletal muscle contraction

Question 17

GABAA receptors activated by amino acid transmitter ____

Answer 17

y-aminobutyric acid (GABA)

Question 18

Binding of GABA > channel opening > influx of Cl- ions > membrane ______, ____ post-synaptic transmission

Answer 18

hyperpolarisation

fast

Question 19

Where do GABAA receptors occur

Answer 19

in CNS, post synaptic inhibition of neuronal activity

Question 20

GABA binding sites located at ______

Answer 20

a/B subunit interfaces

Question 21

Where do synaptic receptors occur?

Answer 21

At synaptic sites within the synaptic cleft

Question 22

What are synaptic receptors activated by?

Answer 22

GABA & mediate phasic inhibition

Lower affinity for GABA & high benzo sensitivity

Question 23

Where do extrasynaptic receptors occur?

Answer 23

Outside synaptic sites

Question 24

What are extrasynaptic receptors activated by?

Answer 24

GABA spillover & mediate tonic inihibition

Higher affinity for GABA & low benzo sensitivity

Question 25

GABA have a widespread distribution in the _____

Answer 25

brain

Question 26

GABA drug examples

Answer 26

benzodiazepines, alcohol, general anaesthetics

Question 27

GABA receptors bind to _____ binding sites

Answer 27

allosteric

positive allosteric modulation

Question 28

Effect is reflected as increased frequency & opening of the receptor _____ ion channel

Answer 28

Cl-