Sensory Transduction & Ion Channels: Thermo-Chemo-Nociceptors

Question 1

What are thermoreceptors?

Answer 1

Thermoreceptors are part of the somatosensory system with sensitive neurites at the end that can sense changes in temperature

Question 2

How do thermoreceptors sense changes in temperature?

Answer 2

They have channels at the tip of neurites which change in shape in response to changes in temperature

These channels are organised in such a way that at certain temperature, the channels open and at other temperature they close

Question 3

What is the Boundary between something feeling warm and painfully hot?

Answer 3

If you touch something that is warm and it gets warmer and warmer, there will come a point at about 45°C where it stops feeling as if it is getting warmer and it gets painfully hot. The thing that happens at this point is that the TRPV1 membrane channel opens. The TRPV1 channels are found only on nociceptive thermoreceptors, which are pain (noxious) receptors.

Question 4

What is the TRP family of ion channels?

Answer 4

Transient Receptor Potential family of ion channels

Many TRP channels are temperature transducers

Question 5

When do TRPV1 channels change shape?

Answer 5

TRPV1 proteins/channels change shape at ~45°C (the temperature at which heat becomes damaging), allowing cations to depolarise the cell, signalling that damage is about to occur

Question 6

Does the ‘hot’ sensation only mean high temperatures?

Answer 6

The sensation of “hot” is not only due to high temperature.

• Inflammation also feels “hot” (e.g. sunburned skin)
• Spicy foods

Question 7

Why does inflammation feel ‘hot’ and painful, even if we lay a cool hand on it and are actually reducing the temperature of the skin?

Answer 7

Injuries e.g. sunburn will produce protons (H+) which triggers the immune response.

• protons attach to the TRPV1 channels
• inflammatory mediators act via various receptors to produce second messengers inside the cell that either:
  a) attach to the TRPV1 channels
  b) phosphorylate the TRPV1 channels

These biochemical adaptations reduce the threshold of the TRPV1 channels so TRPV1 channels open at lower temperatures

• when they open, cell depolarises
• Ca2+ influx (second messenger)
• cells also release pro-inflammatory peptides which further enhance the immune response, which of course produces yet more TRPV1 activation (positive feedback)
• inflammation also upregulates TRPV1 expression to make the cell more sensitive

Question 8

Where else is the upregulation and sensitisation of TRPV1 channels found?

Answer 8

Upregulation and sensitisation of TRPV1 channels is found in neuropathy, and if it becomes self-sustaining it may result in neurogenic pain.

-even if you have an injury which heals, occasionally you still feel neurogenic pain. It is thought that this mechanism might be maintaining this pain response, even though there is no longer an injury, because you still have activation of the TRPV1 channels

Question 9

How do spicy foods taste ‘hot’?

Answer 9

The reason for spicy foods tasting “hot” is because of capsaicin. Capsaicin is a vanilloid.

Capsaicin is produced by plants to protect themselves (rather ironically) against being eaten by mammals. It does so by mimicking one of the inflammatory mediators that stimulate TRPV1.

Question 10

When do TRPV1 channels open?

Answer 10

· Temperatures >45°C
· At lower temperatures, in the presence of inflammatory mediators or H+ ions
· Bound to botanical “warning” chemicals of the vanilloid family (e.g. capsaicin)

When TRPV1 channels open, stuff feels painfully hot