Yes / 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 H2S is a modulator of low voltage-activated T-type Ca2+ channels, and discriminates between the different subtypes of T-type Ca2+ channel in that it selectively modulates Cav3.2, whilst Cav3.1 and Cav3.3 are unaffected. At high concentrations, H2S augments Cav3.2 currents, an observation which has led to the suggestion that H2S exerts its pro-nociceptive effects via this channel, since Cav3.2 plays a central role in sensory nerve excitability. However, at more physiological concentrations, H2S 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 H2S 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 H2S modulation of T-type Ca2+ 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 Ca2+ channel modulation by H2S might be exploited as a novel approach to pain management. / This work was supported by grants from the British Heart Foundation, the Medical Research Council, and the Hebei Medical University
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/12201 |
| Date | 25 January 2016 |
| Creators | Elies, Jacobo, Scragg, J.L., Boyle, J.P., Gamper, N., Peers, C. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | © 2016 Wiley Periodicals, Inc. Full-text reproduced in accordance with the publisher's self-archiving policy. This is the peer reviewed version of the following article: Elies J, Scragg JL, Boyle JP, Gamper N and Peers C (2016) Regulation of the T-type Ca2+ channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2S in nociception. The Journal of Physiology. 594(15): 4119-4129, which has been published in final form at http://dx.doi.org/10.1113/JP270963. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving., Unspecified |
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