Chapter title |
T-Type Ca2+ Channel Regulation by CO: A Mechanism for Control of Cell Proliferation
|
---|---|
Chapter number | 33 |
Book title |
Arterial Chemoreceptors in Physiology and Pathophysiology
|
Published in |
Advances in experimental medicine and biology, January 2015
|
DOI | 10.1007/978-3-319-18440-1_33 |
Pubmed ID | |
Book ISBNs |
978-3-31-918439-5, 978-3-31-918440-1
|
Authors |
Duckles, Hayley, Al-Owais, Moza M., Elies, Jacobo, Johnson, Emily, Boycott, Hannah E., Dallas, Mark L., Porter, Karen E., Boyle, John P., Scragg, Jason L., Peers, Chris, Hayley Duckles, Moza M. Al-Owais, Jacobo Elies, Emily Johnson, Hannah E. Boycott, Mark L. Dallas, Karen E. Porter, John P. Boyle, Jason L. Scragg, Chris Peers |
Abstract |
T-type Ca(2+) 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 Fe(2+) 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 Ca(2+) 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 Ca(2+) 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 [Ca(2+) ]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 Ca(2+) 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 Ca(2+) 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 Ca(2+) channels. |
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Unknown | 1 | 100% |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 10 | 100% |
Demographic breakdown
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Student > Doctoral Student | 2 | 20% |
Lecturer > Senior Lecturer | 1 | 10% |
Other | 1 | 10% |
Lecturer | 1 | 10% |
Student > Bachelor | 1 | 10% |
Other | 2 | 20% |
Unknown | 2 | 20% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 5 | 50% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 10% |
Neuroscience | 1 | 10% |
Agricultural and Biological Sciences | 1 | 10% |
Unknown | 2 | 20% |