T-type Ca2+ channel regulation by CO: a mechanism for control of cell proliferation
Publication date
2015Author
Duckles, H.Al-Owais, M.M.
Elies, Jacobo

Johnson, E.
Boycott, H.E.
Dallas, M.L.
Porter, K.E.
Boyle, J.P.
Scragg, J.L.
Peers, C.
Peer-Reviewed
YesOpen Access status
closedAccess
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T-type Ca2+ channels regulate proliferation in a number of tissue types, including vascular smooth muscle and various cancers. In such tissues, up-regulation of the inducible enzyme heme oxygenase-1 (HO-1) is often observed, and hypoxia is a key factor in its induction. HO-1 degrades heme to generate carbon monoxide (CO) along with Fe2+ and biliverdin. Since CO is increasingly recognized as a regulator of ion channels (Peers et al. 2015), we have explored the possibility that it may regulate proliferation via modulation of T-type Ca2+ channels. Whole-cell patch-clamp recordings revealed that CO (applied as the dissolved gas or via CORM donors) inhibited all 3 isoforms of T-type Ca2+ channels (Cav3.1-3.3) when expressed in HEK293 cells with similar IC50 values, and induction of HO-1 expression also suppressed T-type currents (Boycott et al. 2013). CO/HO-1 induction also suppressed the elevated basal [Ca2+ ]i in cells expressing these channels and reduced their proliferative rate to levels seen in non-transfected control cells (Duckles et al. 2015). Proliferation of vascular smooth muscle cells (both A7r5 and human saphenous vein cells) was also suppressed either by T-type Ca2+ channel inhibitors (mibefradil and NNC 55-0396), HO-1 induction or application of CO. Effects of these blockers and CO were non additive. Although L-type Ca2+ channels were also sensitive to CO (Scragg et al. 2008), they did not influence proliferation. Our data suggest that HO-1 acts to control proliferation via CO modulation of T-type Ca2+ channels.Version
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Duckles H, Al-Owais MM, Elies J et al (2015)T-type Ca2+ channel regulation by CO: a mechanism for control of cell proliferation. In: Peers C, Kumar P, Wyatt C et al (Eds.) Arterial chemoreceptors in physiology and pathophysiology. London: Springer.Link to Version of Record
https://doi.org/10.1007/978-3-319-18440-1_33Type
Book chapterae974a485f413a2113503eed53cd6c53
https://doi.org/10.1007/978-3-319-18440-1_33