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Inhibition of T-type Ca2+ Channels by Hydrogen Sulfide

  • Jacobo Elies
  • Jason L. Scragg
  • Mark L. Dallas
  • Dongyang Huang
  • Sha Huang
  • John P. Boyle
  • Nikita Gamper
  • Chris Peers
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)

Abstract

T-type Ca2+ channels are a distinct family of low voltage-activated Ca2+ channels which serve many roles in different tissues. Several studies have implicated them, for example, in the adaptive responses to chronic hypoxia in the cardiovascular and endocrine systems. Hydrogen sulfide (H2S) was more recently discovered as an important signalling molecule involved in many functions, including O2 sensing. Since ion channels are emerging as an important family of target proteins for modulation by H2S, and both T-type Ca2+ channels and H2S are involved in cellular responses to hypoxia, we have investigated whether recombinant and native T-type Ca2+ channels are a target for modulation by H2S. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS, selectively inhibits Cav3.2 T-type Ca2+ channels heterologously expressed in HEK293 cells, whilst Cav3.1 and Cav3.3 channels were unaffected. Sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive extracellular residue H191, which is also required for tonic binding of Zn2+ to this channel. Chelation of Zn2+ using TPEN prevented channel inhibition by H2S. H2S also selectively inhibited native T-type channels (primarily Cav3.2) in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for H2S regulation, the T-type Ca2+ channel Cav3.2. Results have important implications for the proposed pro-nociceptive effects of this gasotransmitter. Implications for the control of cellular responses to hypoxia await further study.

Keywords

Hydrogen sulfide T-type Ca2+ channel HEK293 cells Sensory neuron Zinc Patch clamp 

Notes

Acknowledgements

This work was supported by The British Heart Foundation.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Jacobo Elies
    • 1
  • Jason L. Scragg
    • 1
  • Mark L. Dallas
    • 2
  • Dongyang Huang
    • 3
  • Sha Huang
    • 3
  • John P. Boyle
    • 1
  • Nikita Gamper
    • 4
  • Chris Peers
    • 1
  1. 1.Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and HealthUniversity of LeedsLeedsUK
  2. 2.School of PharmacyUniversity of ReadingReadingUK
  3. 3.Department of PharmacologyHebei Medical UniversityShijiazhuangChina
  4. 4.School of Biomedical Sciences, Faculty of Biological SciencesUniversity of LeedsLeedsUK

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