title: Quarky calcium release in the heart.
abstract: BACKGROUND
  In cardiac myocytes, "Ca(2+) sparks" represent the stereotyped elemental unit of Ca(2+) release arising from activation of large arrays of ryanodine receptors (RyRs), whereas "Ca(2+) blinks" represent the reciprocal Ca(2+) depletion signal produced in the terminal cisterns of the junctional sarcoplasmic reticulum. Emerging evidence, however, suggests possible substructures in local Ca(2+) release events.
  
  
  OBJECTIVE
  With improved detection ability and sensitivity provided by simultaneous spark-blink pair measurements, we investigated possible release events that are smaller than sparks and their interplay with regular sparks.
  
  
  RESULTS
  We directly visualized small solitary release events amid noise: spontaneous Ca(2+) quark-like or "quarky" Ca(2+) release (QCR) events in rabbit ventricular myocytes. Because the frequency of QCR events in paced myocytes is much higher than the frequency of Ca(2+) sparks, the total Ca(2+) leak attributable to the small QCR events is approximately equal to that of the spontaneous Ca(2+) sparks. Furthermore, the Ca(2+) release underlying a spark consists of an initial high-flux stereotypical release component and a low-flux highly variable QCR component. The QCR part of the spark, but not the initial release, is sensitive to cytosolic Ca(2+) buffering by EGTA, suggesting that the QCR component is attributable to a Ca(2+)-induced Ca(2+) release mechanism. Experimental evidence, together with modeling, suggests that QCR events may depend on the opening of rogue RyR2s (or small cluster of RyR2s).
  
  
  CONCLUSIONS
  QCR events play an important role in shaping elemental Ca(2+) release characteristics and the nonspark QCR events contribute to "invisible" Ca(2+) leak in health and disease.
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD, USA. dbrochet@umaryland.edu
authors.forename: Didier X P
authors.initials: DX
authors.lastname: Brochet
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xie
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yang
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
authors.forename: W Jonathan
authors.initials: WJ
authors.lastname: Lederer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D019837:Ryanodine Receptor Calcium Release Channel; D004533:Egtazic Acid; D002118:Calcium