title: Cellular alternans: a mechanism linking calcium cycling proteins to cardiac arrhythmogenesis.
abstract: Essentially all previous research on alternans has been restricted to normal myocardium, whereas sudden cardiac death (SCD) occurs most commonly in patients with ventricular dysfunction (i.e., heart failure), which is associated with marked disruption of proteins responsible for normal calcium cycling in myocytes. Several lines of evidence from studies in normal hearts suggest a link between impaired calcium cycling which characterizes ventricular mechanical dysfunction and impaired calcium cycling that is responsible for alternans. In normal myocardium, cells which exhibit the slowest calcium cycling, and not the slowest repolarization, are most susceptible to alternans. Decreased expression of key calcium cycling proteins is observed in alternans-prone cells. Sarcoplasmic reticulum ATPase (SERCA2a) expression is decreased, suggesting a mechanism for the slower sarcoplasmic reticulum (SR) calcium reuptake observed in alternans-prone cells. In addition, diminished ryanodine receptor (RyR) function leading to abnormal calcium release from the SR is also linked to cellular alternans. Although impaired contractile function clearly predisposes to SCD, the mechanisms linking mechanical to electrophysiological dysfunction in the heart are unclear. We propose that cellular calcium alternans may be an important mechanism linking mechanical dysfunction to cardiac arrhythmogenesis.
authors.affiliation: MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Drive, Hamann 330, Cleveland, OH 44109-1998, USA.
authors.forename: Lance D
authors.initials: LD
authors.lastname: Wilson
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wan
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016757:Death, Sudden, Cardiac; D005936:Glucans / Q000378:metabolism; D006801:Humans
chemical_list: D015415:Biomarkers; D005936:Glucans; C439358:alternan; D002118:Calcium