title: Dynamic calcium movement inside cardiac sarcoplasmic reticulum during release.
abstract: BACKGROUND
  Intra-sarcoplasmic reticulum (SR) free [Ca] ([Ca](SR)) provides the driving force for SR Ca release and is a key regulator of SR Ca release channel gating during normal SR Ca release or arrhythmogenic spontaneous Ca release events. However, little is known about [Ca](SR) spatiotemporal dynamics.
  
  
  OBJECTIVE
  To directly measure local [Ca](SR) with subsarcomeric spatiotemporal resolution during both normal global SR Ca release and spontaneous Ca sparks and to evaluate the quantitative implications of spatial [Ca](SR) gradients.
  
  
  RESULTS
  Intact and permeabilized rabbit ventricular myocytes were subjected to direct simultaneous measurement of cytosolic [Ca] and [Ca](SR) and FRAP (fluorescence recovery after photobleach). We found no detectable [Ca](SR) gradients between SR release sites (junctional SR) and Ca uptake sites (free SR) during normal global Ca release, clear spatiotemporal [Ca](SR) gradients during isolated Ca blinks, faster intra-SR diffusion in the longitudinal versus transverse direction, 3- to 4-fold slower diffusion of fluorophores in the SR than in cytosol, and that intra-SR Ca diffusion varies locally, dependent on local SR connectivity. A computational model clarified why spatiotemporal gradients are more detectable in isolated local releases versus global releases and provides a quantitative framework for understanding intra-SR Ca diffusion.
  
  
  CONCLUSIONS
  Intra-SR Ca diffusion is rapid, limiting spatial [Ca](SR) gradients during excitation-contraction coupling. Spatiotemporal [Ca](SR) gradients are apparent during Ca sparks, and these observations constrain models of dynamic Ca movement inside the SR. This has important implications for myocyte SR Ca handling, synchrony, and potentially arrhythmogenic spontaneous contraction.
authors.affiliation: Department of Pharmacology, University of California-Davis, 451 Health Sciences Drive, Davis, CA 95616, USA.
authors.forename: Eckard
authors.initials: E
authors.lastname: Picht
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Zima
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Shannon
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Duncan
authors.forename: Lothar A
authors.initials: LA
authors.lastname: Blatter
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D023421:Models, Animal; D008962:Models, Theoretical; D009119:Muscle Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002118:Calcium