H2S does not regulate proliferation via T-type Ca2+ channels

Abstract

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.

Regulation of Coronary Blood Flow

“…T-type channels are not expressed in the coronary smooth muscle cells of rabbits (647), dogs (130, 571), pigs (95, 358), or humans (776). While not present in the primary myocytes, T-type channels appear during the culture of human coronary smooth muscle cells, which may represent a phenotypic change elicited by an artificial environment (305,776). T-type channels are, however, normally expressed in the coronary smooth muscle of guinea pigs (366) and mice (156).…”

Hydrogen Sulfide (H2S)-Releasing Compounds: Therapeutic Potential in Cardiovascular Diseases

“…T-type channels (Cav3.1, 3.2, and 3.3) obviously affect the proliferation of VSMCs and H 2 S selectively inhibits T-channel Cav3.2. H 2 S induces concentration-dependent proliferation inhibition in the human coronary artery smooth muscle cells and smooth muscle cell line A7r5, however, this mechanism of suppressing cell proliferation is independent of selective inhibition of T-type channels by H 2 S ( Elies et al, 2015 ). H 2 S reduces myogenic tension and causes relaxation of the phenylephrine (PE) mesenteric artery.…”