Membrane-Bound Receptors: Ligand gated ion channels and G-Protein Coupled Receptors

Question 1

What is a Receptor:

Answer 1

A protein or group of proteins, usually embedded in the cell membrane, that allows the cell to collect information about its surroundings

Question 2

What is a Ligand:

Answer 2

A chemical messenger (can be a small molecule or peptide) that binds and stabilizes a conformation of the receptor

Question 3

Describe Conformational change:

Answer 3

change in the shape of a receptor that induces some downstream signal transduction

Question 4

Properties of Receptors physiologically

Answer 4

1. Receptors are normal points of control of physiologic processes.
2. Under physiologic conditions, receptor function is regulated by molecules supplied by the body.
3. Drugs can only mimic or block the body’s own regulatory molecules they will not give a cell new function

Question 5

What are Agonists

Answer 5

drug combines with receptor to stimulate target organ

Question 6

What are Antagonists

Answer 6

drug combines with receptor, but interferes with a naturally occurring agonist or an agonist drug

Question 7

A ligand that binds to a receptor, thereby activating it is called an

Answer 7

agonist.

Question 8

A ligand that binds to a receptor that prevents it from activating is called

Answer 8

an antagonist.

Question 9

How does Orthosteric antagonist act?

Answer 9

They act on the main binding site of the receptor

Question 10

How does Allosteric antagonist act?

Answer 10

They act on an accessory binding site of the receptor

Question 11

How does Pore blocker act?

Answer 11

Physically obstructs the channel (ion channels)

Question 12

Most receptors fluctuate between different natural conformations , some conformations are associated with pharmacologic activity and some are not. What are these activity?

Answer 12

Active
Partially active
Inactive

Question 13

Drugs can activate or inactivate receptors by stabilizing a pharmacologically significant conformation by binding to the same site as the endogenous compound is called

Answer 13

orthosteric site

Question 14

Drugs can activate or inactivate receptors by stabilizing a pharmacologically significant conformation by binding to an alternative site

Answer 14

allosteric site

Question 15

ligand gated ion channels:
Location
Effector site
Coupling
Examples
Structure

Answer 15

Location:
membrane

Effector site: Ion Channel

Coupling: Direct

Examples:
Nicotinic acetylcholine receptor, GABAa

Structure:
Oligomeric assembly of subunits surrounding central pore

Question 16

G protein-coupled receptors
Location
Effector site
Coupling
Examples
Structure

Answer 16

Location: Membrane

Effector site: Channel or enzyme

Coupling: G protein or arrenstin

Examples: Muscarinic acetylcholine receptor, adrenoreceptors

Structure: Monomeric or oligomeric assembly of subunits comprising seven transmembrane helices with intracellular G-protein- coupling domain

Question 17

what is resting membrane potential

Answer 17

Resting membrane potential: Inside of the cell has an overall negative charge of ~-70 mV

Question 18

what is cell excitatory

Answer 18

Excitatory: means that the inside of the cell’s charge approaches 0 mV
Generally by letting positive ions into the cell

Question 19

What is cell inhibitory

Answer 19

Inhibitory: means that the inside of the cell’s charge becomes more negative
Generally by letting negative ions (mainly chloride) into of the cell

Question 20

Characteristics of ligand gated ion channels

Answer 20

1. Fast transmission
2. Composed of several subunits arranged around a central ion pore
   - - Agonist binding opens pore
3. Major families:
   - - Cys-loop receptors: nicotinic acetylcholine receptor, glycine receptors, 5HT-3 receptor, etc.
   - - Ionotropic Glutamate Receptors: AMPA receptor, NMDA receptor, kainate receptor

Question 21

What are cys-loop receptors? Describe.

Answer 21

1. Named for the loop formed by the disulfide bond between two cysteines near the N-terminus
2. Made of five subunits arranged around a central pore
3. Five types of subunits: α, β, γ, δ, ε
4. Excitatory: Nicotinic acetylcholine receptors, serotonin receptors
5. Inhibitory: Glycine and GABAA

Question 22

How does happen gating in cys-loop receptor

Answer 22

The second transmembrane domain of the α subunit generally obstructs the ion pore
Agonist binding changes the conformation, moving the obstruction and allowing ions to flow though

Question 23

Drugs that act on ligand-gated ion channels

Answer 23

1. Cys-loop receptors
   - - Nicotinic acetylcholine receptors: Nicotine, Varenicline (Chantix)
   - - GABAA receptors: Ambien (zolpidem)Barbituates, benzodiazepines, alcohol
2. Glutamate Receptors
   - - NMDA receptors: Ketamine
   - - AMPA receptors: Aniracetam (cognition-enhancer)

Question 24

cys-loop receptors includes excitatory and inhibitory receptors. List these receptors excitatory and inhibitory receptors.

Answer 24

Excitatory: Nicotinic acetylcholine receptors: Nicotine, Varenicline (Chantix)
Inhibitory: GABAa receptors: Ambien (zolpidem)Barbituates, benzodiazepines, alcohol

Question 25

List Glutamate Receptors

Answer 25

1. NMDA receptors: Ketamine | 2. AMPA receptors: Aniracetam (cognition-enhancer)

Question 26

Where do Nicotinic Acetylcholine Receptors exist?

Answer 26

Exist at the neuromuscular junction (NMJ) and in the CNS

Question 27

NMJ contain what subunits

Answer 27

contain a, β, δ, and γ subunits

Question 28

Neuronal nAChRs contain which subunits

Answer 28

Neuronal nAChRs contain only a and β subunits

Question 29

Excitatory Nicotinic Acetylcholine Receptors pass which ions

Answer 29

Pass Na+, K+, and some Ca++ ions

Question 30

Nicotinic Acetylcholine Receptors are composed of how many subunits

Answer 30

Composed of five subunits

Question 31

In the brain, nAChRs upregulate in response to chronic use of hint (like smoking)

Answer 31

nicotine

Question 32

Ionotropic Glutamate Receptors are?

Answer 32

1. AMPA receptors 2. NMDA receptors 3. Kainate receptors

Question 33

Excitatory Ionotropic Glutamate Receptors pass what ions?

Answer 33

Pass Na+ and K+ ions | NMDA receptors can also pass Ca++ ions

Question 34

Ionotropic Glutamate Receptors are composed of how many subunits

Answer 34

Composed of four subunits Each subunit has four transmembrane domains -- Second TM domain forms the ion pore

Question 35

Each subunit of Ionotropic Glutamate Receptors has a binding site but not all binding sites are for glutamate

Answer 35

Each subunit of Ionotropic Glutamate Receptors has a binding site but not all binding sites are for glutamate

Question 36

NMDA receptor: two binding sites for glutamate, two binding sites for glycine All four binding sites must be occupied for the channel to open

Answer 36

NMDA receptor: two binding sites for glutamate, two binding sites for glycine All four binding sites must be occupied for the channel to open

Question 37

What is Long Term Potentiation (LTP):

Answer 37

Long Term Potentiation (LTP): the more often a neuron fires, the “stronger” the synapse gets -- Implicated in learning and memory

Question 38

At resting membrane potential, NMDA receptors are blocked by

Answer 38

Mg++ Magnesium block is voltage dependent Depolarization of neuron relieves the block, allows NMDAR to open

Question 39

NMDARs pass Ca++, which activates Calmodulin Kinase II (CaMKII), which leads to AMPARs inserted into the synapse More AMPARs = stronger synapse NMDARs are “coincidence detectors

Answer 39

NMDARs pass Ca++, which activates Calmodulin Kinase II (CaMKII), which leads to AMPARs inserted into the synapse More AMPARs = stronger synapse NMDARs are “coincidence detectors

Question 40

What are the three main classes of G Protein-Coupled Receptors (GPCRs)

Answer 40

1. Class A: adrenergic receptors, muscarinic acetylcholine receptors 2. Class B: Parathyroid Hormone receptor 3. Class C: metabotropic glutamate receptors, GABAB receptors

Question 41

G Protein-Coupled Receptors (GPCRs) are slower than ligand gated ion channels. What do they rely on for signaling

Answer 41

Slower signaling than ligand-gated ion channels Rely on second messengers for signaling ~3% of our genome dedicated to GPCR coding