title: Regulation of the T-type Ca(2+) channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2 S in nociception.
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/affinity of this binding site. This review discusses the different reports of H2 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 H2 S might be exploited as a novel approach to pain management.
authors.affiliation: Faculty of Medicine and Health, University of Leeds, Leeds, UK.
authors.forename: Jacobo
authors.initials: J
authors.lastname: Elies
authors.affiliation: Faculty of Medicine and Health, University of Leeds, Leeds, UK.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Scragg
authors.affiliation: Faculty of Medicine and Health, University of Leeds, Leeds, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Boyle
authors.affiliation: Faculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds, UK.|Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Nikita
authors.initials: N
authors.lastname: Gamper
authors.affiliation: Faculty of Medicine and Health, University of Leeds, Leeds, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Peers
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D059225:Nociception / Q000502:physiology*
chemical_list: D020747:Calcium Channels, T-Type; D006862:Hydrogen Sulfide