Membrane Bound Receptors

Question 1

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

Ligand

Answer 2

a chemical messenger (small molecule or peptide) that induces conformational change in the receptor

Question 3

Conformational change

Answer 3

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

Question 4

Types of receptors

Answer 4

1. Ligand gated ion channels

2. G protein coupled receptors

Question 5

Action Potential

Answer 5

How cells communicate w/ one another; neurons, muscle cells & cardiac cells all produce action potentials

Question 6

Excitatory

Answer 6

charge approaches 0mV inside the cell by letting positive ions into the cell (sodium or calcium)

Resting membrane potential -70mV overall charge inside the cell

Question 7

Inhibitory

Answer 7

the charge becomes more negative inside the cell by letting negative ions (mainly chloride) in

Question 8

Agonist

Answer 8

A ligand that binds to a receptor activating it

2 Types

1. Orthosteric agonist
2. Allosteric agonist

Question 9

Antagonist

Answer 9

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

3 Types

1. Orthosteric antagonist - acts on main binding site of the receptor
2. Allosteric antagonist - acts on an accessory binding site of the receptor
3. Pore channel - physically obstructs the channel (ion channels)

Question 10

Ligand gated ion channel

Answer 10

Fast transmission
Composed of several subunits arranged around a central pore
> Agonist binding open pore

Major families:
> Cys-loops receptors:
 nicotinic acetylcholine receptor
glycine receptors
5HT-3 receptor

Ionotropic glutamate receptors:
AMPA receptor
NMDA receptor
kainate receptor

Question 11

Cys Loop receptors

Answer 11

> Named for the loop formed by the disulfide bond bw two cysteines near the N-terminus
Made of 5 subunits arranged around a central pore
5 types of subunits: alpha, beta, gamma, delta, epsilon
Excitatory: Nicotinic acetylcholine receptors, serotonin receptors
Inhibitory: Glycine & GABA-A

Question 12

Gating

Answer 12

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

Question 13

Drugs that act on ligand gated channels

Answer 13

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

Question 14

Nicotinic Acetylcholine Receptors

Answer 14

> Exist at the neuromuscular junction (NMJ) & in the CNS

• NMJ mAChR contains alpha, beta, delta, gamma subunits
• Neuronal nAChRs contain only alpha & beta subunits

> Excitatory
-Pass Na+, K+ & some Ca++ ions

> Composed of 5 subunits
In the brain, nAChRs upregulate in response to chronic nicotine (like smoking)

Question 15

Ionotropic Glutamate Receptors

Answer 15

> AMPA receptors
NMDA receptors
Kainate receptors

> Excitatory

• Pass Na+ & K+ ions
• NMDA receptors can also pass Ca++

> Composed of 4 subunits

• Each subunit has 4 transmembrane domains
• Second TM domain forms the ion pore

> Each subunit has a binding site-not all binding sites are for glutamate

• NMDA receptor: 2 binding sites for glutamate, 2 binding sites for glycine
• All 4 binding sites must be occupied for the channel to open

Question 16

Long Term Potentiation

Answer 16

> Long Term Potentiation (LTP): the more often a neuron fires, the ‘stronger’ the synpse gets
-Implicated in learning & memory

> At resting membrane potential, NMDA receptors are blocked by Mg++

• Mg block is voltage dependent
• Depolarization of neuron relieves the block, allows NMDR to open

> NMDRs pass Ca++, which activates CaMKII, which leads to AMPARs inserted into the synapse
-More AMPAR’s = stronger synapse

> NMDARs are ‘coincidence detectors’

Question 17

G Protein Coupled Receptors

GPCRs

Answer 17

> Slower signaling that ligand gated ion channels
-Rely on 2nd messengers for signaling

> ~3% of our genome dedicated to GPCR coding
Target for more than half of current drugs
3 main classes
-Class A: adrenergic receptors, muscarinic acetylcholine receptors
-Class B: Parathyroid Hormone receptor
-Class C: metabotropic glutamate receptors, GABA-B receptors

Question 18

G-a subunits

Answer 18

> G-s - activation of adenylyl cyclase & increase in cAMP
G-i - inhibition of adenylyl cyclase & decrease in cAMP
G-q - activation of phospholipase C, phosphoinositol hydrolysis, increase in IP3 & DAG & release of Ca++ from intracellular stores

Question 19

Cholera Toxin Mechanism

Answer 19

> Cholera toxin is internalized by the cell
Disrupts conversion of GTP to GDP
Increased level of GTP leads to abnormally high cAMP levels
-Activates chloride ion pumps, which release more Cl- into the intestinal lumen
-Na+, K+, bicarb ions follow, then leading to more water being held in the intestine to balance osmolarity

Question 20

GPCR Desensitization

Answer 20

> If a ligand is bound onto a GPCR for a prolonged period of time, B-arrestin binds to the receptor, thus tagging it for internalization
-Contributes to drug tolerance

> The GPCR-B-arrestin complex can act as a protein scaffold inside the cell
Independent of G protein signaling