H2S does not regulate proliferation via T-type Ca2+ channels.
T-type Ca(2+) channels (Cav3.1, 3.2 and 3.3) strongly influence proliferation of various cell types, including vascular smooth muscle cells (VSMCs) and certain cancers. We have recently shown that the gasotransmitter carbon monoxide (CO) inhibits T-type Ca(2+) channels and, in so doing, attenuates proliferation of VSMC. We have also shown that the T-type Ca(2+) channel Cav3.2 is selectively inhibited by hydrogen sulfide (H2S) whilst the other channel isoforms (Cav3.1 and Cav3.3) are unaffected. Here, we explored whether inhibition of Cav3.2 by H2S could account for the anti-proliferative effects of this gasotransmitter. H2S suppressed proliferation in HEK293 cells expressing Cav3.2, as predicted by our previous observations. However, H2S was similarly effective in suppressing proliferation in wild type (non-transfected) HEK293 cells and those expressing the H2S insensitive channel, Cav3.1. Further studies demonstrated that T-type Ca(2+) channels in the smooth muscle cell line A7r5 and in human coronary VSMCs strongly influenced proliferation. In both cell types, H2S caused a concentration-dependent inhibition of proliferation, yet by far the dominant T-type Ca(2+) channel isoform was the H2S-insensitive channel, Cav3.1. Our data indicate that inhibition of T-type Ca(2+) channel-mediated proliferation by H2S is independent of the channels' sensitivity to H2S.
Division of Cardiovascular and Diabetes Research, LICAMM, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
Jacobo
J
Elies
Division of Cardiovascular and Diabetes Research, LICAMM, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
Emily
E
Johnson
Division of Cardiovascular and Diabetes Research, LICAMM, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
John P
JP
Boyle
Division of Cardiovascular and Diabetes Research, LICAMM, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
Jason L
JL
Scragg
Division of Cardiovascular and Diabetes Research, LICAMM, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK. Electronic address: c.s.peers@leeds.ac.uk.
Chris
C
Peers
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D020747:Calcium Channels, T-Type; D002118:Calcium; D006862:Hydrogen Sulfide
Gasotransmitter; Hydrogen sulfide; Proliferation; T-type calcium channel; Vascular smooth muscle