Regulation of the T-type Ca(2+) channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2 S in nociception

The Journal of Physiology
Jacobo EliesChris Peers

Abstract

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 H2 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, H2 S augments Cav3.2 currents, an observation which has led to the suggestion that H2 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, H2 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 H2 S may act in a novel manner to alter channel activity by potentiating the zinc sensitivity/affin...Continue Reading

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Citations

Sep 20, 2018·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Xiaomeng XuChuanyong Liu
Mar 20, 2020·The Journal of Biological Chemistry·Dongyang HuangNikita Gamper
Aug 2, 2016·The Journal of Physiology·Mark L Dallas
May 4, 2018·Pflügers Archiv : European journal of physiology·Ricardo de PascualAntonio M G de Diego
Dec 15, 2020·Biotechnology and Applied Biochemistry·Menglan Wang, Baskaran Thyagarajan

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