doi: 10.1161/01.RES.0000093184.27194.42
© 2003 American Heart Association, Inc.
Editorials |
Not All Sudden Death Is the Same
From the Department of Anesthesia, Brigham and Women’s Hospital, Boston, Mass.
Correspondence to P.D. Allen, MD, PhD, Professor of Anesthesia, Department of Anesthesia, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail allen@zeus.bwh.harvard.edu
Key Words: sudden death • sarcoplasmic reticulum • ryanodine receptors • ventricular tachycardia • FKBP12.6
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Sudden death as a result of cardiac arrhythmia is probably the most common symptom associated with cardiac disease. It occurs not only in people with known cardiac disease, most notably congestive heart failure, but also in young, apparently healthy individuals who have no apparent structural heart disease. Frequently, in this latter group, these fatal arrhythmias are associated with exercise and increased ß-adrenergic stimulation. One possible mechanism for how these arrhythmias could occur in otherwise "normal" individuals is an aberrant release of Ca2+ from the sarcoplasmic reticulum (SR), which in turn could cause delayed afterdepolarizations1 that can trigger potentially fatal ventricular arrhythmias.
Unlike skeletal muscle, where excitation-contraction coupling (EC coupling) is intermittent and mediated through a mechanical coupling between the slow voltage-gated Ca2+ channel (dihydropyridine receptor, DHPR) in the sarcolemma and the skeletal isoform of the large-conductance calcium release channel in the SR (ryanodine receptor, RyR), RyR1 in cardiac muscle EC coupling is rhythmic and the cardiac isoform of RyR (RyR2) is activated by the inward Ca2+ influx through the cardiac DHPR via Ca2+-induced Ca2+ release (CICR).2 In the heart, RyR2 does not act in a vacuum but rather is part of a macromolecular complex containing the immunophilin FKBP12.6, phosphorylases, and phosphatases,3 in addition to the DHPR and several other proteins including calsequestrin, triadin, junctin, and junctophilin, to name only a few, that make up the calcium release unit (CRU).4 Heart failure has been associated with disruption of this macromolecular complex secondary to hyperphosphorylation of RyR2 and the associated dissociation
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