Transduction of pain signals, ion channels and GPCRs

Question 1

Inotropic

Answer 1

Ligand-gated channels

Question 2

Metabotropic

Answer 2

G-protein-coupled receptors

-receptor modulates channels or other intracellular effects

Question 3

Sensory afferent for temperature and pain have specialized receptors nerve endings that detect specific stimuli. what are the thermal and chemical receptors?

Answer 3

Thermal 
-TRPV1
-TRPM8
-TRPA1
Chemical 
-P2X
-ASIC
TRPV1

Question 4

Ionotropic receptors characteristics?

Answer 4

• Comprised of 4-5 protein subunits

- Mediate rapid postsynaptic effects

Question 5

Glutamate receptors are?

Answer 5

NMDA

AMPA/Kainate

Question 6

What Cys-loop receptors are?

Answer 6

• Nicotinic acetylcjoline receptor (nAChr)
• 5-HT3 receptor
• GABAa receptor
• Glycine receptor

Question 7

AMPA receptor?

Answer 7

-Glu R1-R4 (Ionotropic glutamates)

Question 8

NMDA receptor?

Answer 8

• Glu R5-R7

- KA1 and KA2

Question 9

GABA receptor?

Answer 9

-Alpha1-7
-Beta1-4
(part of the Cys-loop)

Question 10

nAch receptor?

Answer 10

-Alpha2-9
-Beta1-4
(part of the Cys-loop)

Question 11

Serotonin

Answer 11

5-HT3

part of the Cys-loop

Question 12

P2X family receptors

Answer 12

• P2X and acid-sensing ion (ASICs)
• Excitatory effect
• Non-selective Na+, K+, and Ca++
• P2X is activated by ATP
• ASIC: activated by H+
• Channels can be Homomeric or Heteromeric

Question 13

P2X subunits are?

Answer 13

P2X1-P2X7

Question 14

ASIC subunits are?

Answer 14

ASIC1-ASIC4

Question 15

Activation of ATP-gated P2X3 channels initiates nociceptive signaling. T/F

Answer 15

-True, P2X3 channels are primary ATP-gated channels expressed by nociceptors.

Question 16

ASIC families?

Answer 16

PH sensors in nociceptors

-Tissue acidosis ischemia, Inflammation, tumors, and lesions.

Question 17

ASIC in primary afferent nociceptors and second order spinal cord neurons are sensitive to?

Answer 17

PH and can increase their sensitivity in response to a number of inflammatory factors.

Question 18

TRPA1 channels?

**

Answer 18

-Activated by garlic and horseradish

Question 19

TRPM8 channels?

**

Answer 19

• Activated by Mint

- Menthol

Question 20

TRPV4 channels?

Answer 20

-Did not mention any activators

Question 21

TRPV3 channels?

Answer 21

-Camphor

Question 22

TRPV1 channels?

***

Answer 22

• chilli

- Capsaicin

Question 23

TRP channels are critical for pain sensing: capsaicin acts

Answer 23

-Exclusively via TRPV1

Question 24

TRPV1 Agonists

Answer 24

-Capsaicin

Question 25

TRPV1 Antagonists as novel analgesics does what?

Answer 25

• They block effectively noxious heat pain, and cause increase in core body temperature.

Question 26

TRPV1 Agonists as analgesics does what?

Answer 26

They cause desensitization of nociceptors with fewer side effects.

Question 27

TRVP3 in keratinocytes transmits temperature via ATP

Answer 27

-Heat simulates TRVP3 channels on the skin cells to release ATP.

Question 28

Heterotrimeric (“large”) G-proteins

Answer 28

• G-protein binds to the receptor
• G- protein is composed of 3 subunit (alpha, beta, gamma)
• Alpha subunit binds to GTP or GDP
• G-protein function as molecular switch (ON=GTP)(OFF=GDP)

Question 29

There are several classes of Ga subunit such as?

Answer 29

• Gsα (stimulatory)
• Giα (inhibitory)
• Gqα

Question 30

G-Protein cycle

Answer 30

1. GDP-bound
2. Ligand interaction
3. conformation changes
4. GDP-GTP exchange
5. Alpha beta,gamma dissociation
6. Termination of signaling by GTPase activity

Question 31

After injury to peripheral nerves, causing neuropathic pain, Nav1.8 ?

Answer 31

Redistributes to the site of the lesion, potentially increasing the number of available sodium channels

Question 32

Nav1.8 contributes to upstroke of action potential?

Answer 32

Rapidly reprimes and can contribute to repetitive firing