title: Ca sparks do not explain all ryanodine receptor-mediated SR Ca leak in mouse ventricular myocytes.
abstract: Diastolic Ca leak from the sarcoplasmic reticulum (SR) of ventricular myocytes reduces the SR Ca content, stabilizing the activity of the SR Ca release channel ryanodine receptor for the next beat. SR Ca leak has been visualized globally using whole-cell fluorescence, or locally using confocal microscopy, but never both ways. When using confocal microscopy, leak is imaged as "Ca sparks," which are fluorescent objects generated by the local reaction-diffusion of released Ca and cytosolic indicator. Here, we used confocal microscopy and simultaneously measured the global ryanodine-receptor-mediated leak rate (J(leak)) and Ca sparks in intact mouse ventricular myocytes. We found that spark frequency and J(leak) are correlated, as expected if both are manifestations of a common phenomenon. However, we also found that sparks explain approximately half of J(leak). Our strategy unmasks the presence of a subresolution (i.e., nonspark) release of potential physiological relevance.
authors.affiliation: Department of Molecular Biophysics & Physiology, Rush University, Chicago, Illinois, USA.
authors.forename: Demetrio J
authors.initials: DJ
authors.lastname: Santiago
authors.forename: Jerald W
authors.initials: JW
authors.lastname: Curran
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
authors.forename: W J
authors.initials: WJ
authors.lastname: Lederer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Stern
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ríos
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Shannon
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D015640:Ion Channel Gating; D051379:Mice; D018613:Microscopy, Confocal; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D015398:Signal Transduction; D018487:Ventricular Dysfunction, Left
chemical_list: D002121:Calcium Channel Blockers; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium