Referenced in: none

Automatically associated channels: Cav3.2

Title: Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels.

Authors: Hayley Duckles, Hannah E Boycott, Moza M Al-Owais, Jacobo Elíes, Emily Johnson, Mark L Dallas, Karen E Porter, Francesca Giuntini, John P Boyle, Jason L Scragg, Chris Peers

Journal, date & volume: Pflugers Arch., 2015 Feb , 467, 415-27

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24744106

Abstract
Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Cav3.2 T-type Ca(2+) channels in HEK293 cells raised basal [Ca(2+)]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca(2+)]i levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca(2+) currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca(2+) channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically.