Aldosterone has recently been identified as a pathogenic stimulus of heart failure. It is produced by cells of the adrenal gland if their intracellular Ca2+ concentration is elevated, such as occurs after stimulation with angiotensin II. Although Ca2+/calmodulin-dependent kinase II (CaMKII) is known to regulate the Ca2+ channels (such as a1H T-type Ca2+ channels) that must be opened to maintain the elevated concentration of intracellular Ca2+ that is required to sustain the production of aldosterone, its mechanism of action had not been determined. Now, in a study appearing online on August 17 in advance of print publication in the September issue of the Journal of Clinical Investigation, Paula Barrett and colleagues from Virginia University School of Medicine have shown that in both activated cells in culture and rats infused with angiotensin II, CaMKII phosphorylates a serine residue of a1H T-type Ca2+ channels, which leads to an increase in the intracellular Ca2+ concentration. Blocking this phosphorylation step in rats decreased the amount of aldosterone produced in response to angiotensin II. This study provides new insight into the molecular mechanisms by which CaMKII regulates a1H T-type Ca2+ channels and might provide new therapeutic approaches to regulating aldosterone production.
TITLE: Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase II
AUTHOR CONTACT:
Paula Q. Barrett
University of Virginia School of Medicine
Charlottesville, Virginia, USA
View the PDF of this article at: https://the-jci/article.php?id=27918
JCI table of contents: August 17, 2006
Contact: Karen Honey
Journal of Clinical Investigation
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