title: Mechano-chemo-transduction in cardiac myocytes.
abstract: The heart has the ability to adjust to changing mechanical loads. The Frank-Starling law and the Anrep effect describe exquisite intrinsic mechanisms the heart has for autoregulating the force of contraction to maintain cardiac output under changes of preload and afterload. Although these mechanisms have been known for more than a century, their cellular and molecular underpinnings are still debated. How does the cardiac myocyte sense changes in preload or afterload? How does the myocyte adjust its response to compensate for such changes? In cardiac myocytes Ca2+is a crucial regulator of contractile force and in this review we compare and contrast recent studies from different labs that address these two important questions. The 'dimensionality' of the mechanical milieu under which experiments are carried out provide important clues to the location of the mechanosensors and the kinds of mechanical forces they can sense and respond to. As a first approximation, sensors inside the myocyte appear to modulate reactive oxygen species while sensors on the cell surface appear to also modulate nitric oxide signalling; both signalling pathways affect Ca2+handling. Undoubtedly, further studies will add layers to this simplified picture. Clarifying the intimate links from cellular mechanics to reactive oxygen species and nitric oxide signalling and to Ca2+handling will deepen our understanding of the Frank-Starling law and the Anrep effect, and also provide a unified view on how arrhythmias may arise in seemingly disparate diseases that have in common altered myocyte mechanics.
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, 95616, USA.|Department of Biomedical Engineering, University of California, Davis, CA, 95616, USA.|Department of Internal Medicine/Division of Cardiology, University of California, Davis, CA, 95616, USA.
authors.forename: Ye
authors.identifier: 0000-0003-4818-9570
authors.initials: Y
authors.lastname: Chen-Izu
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, 95616, USA.
authors.forename: Leighton T
authors.initials: LT
authors.lastname: Izu
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002118:Calcium
keywords: calcium signalling; cardiac arrhythmia; cardiac myocytes; heart disease; mechanotransduction; muscle mechanics; nitric oxide synthase; reactive oxygen species