Loading…
Regulation of the T‐type Ca 2+ channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H 2 S in nociception
Ion channels represent a large and growing family of target proteins regulated by gasotransmitters such as nitric oxide, carbon monoxide and, as described more recently, hydrogen sulfide. Indeed, many of the biological actions of these gases can be accounted for by their ability to modulate ion chan...
Saved in:
| Published in: | The Journal of physiology 2016-08, Vol.594 (15), p.4119-4129 |
|---|---|
| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Ion channels represent a large and growing family of target proteins regulated by gasotransmitters such as nitric oxide, carbon monoxide and, as described more recently, hydrogen sulfide. Indeed, many of the biological actions of these gases can be accounted for by their ability to modulate ion channel activity. Here, we report recent evidence that H
2
S is a modulator of low voltage‐activated T‐type Ca
2+
channels, and discriminates between the different subtypes of T‐type Ca
2+
channel in that it selectively modulates Cav3.2, whilst Cav3.1 and Cav3.3 are unaffected. At high concentrations, H
2
S augments Cav3.2 currents, an observation which has led to the suggestion that H
2
S exerts its pro‐nociceptive effects via this channel, since Cav3.2 plays a central role in sensory nerve excitability. However, at more physiological concentrations, H
2
S is seen to inhibit Cav3.2. This inhibitory action requires the presence of the redox‐sensitive, extracellular region of the channel which is responsible for tonic metal ion binding and which particularly distinguishes this channel isoform from Cav3.1 and 3.3. Further studies indicate that H
2
S may act in a novel manner to alter channel activity by potentiating the zinc sensitivity/affinity of this binding site. This review discusses the different reports of H
2
S modulation of T‐type Ca
2+
channels, and how such varying effects may impact on nociception given the role of this channel in sensory activity. This subject remains controversial, and future studies are required before the impact of T‐type Ca
2+
channel modulation by H
2
S might be exploited as a novel approach to pain management.
image |
|---|---|
| ISSN: | 0022-3751 1469-7793 |
| DOI: | 10.1113/JP270963 |