title: Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low.
abstract: The sarcoplasmic reticulum (SR) in ventricular myocytes contains releasable Ca(2+) for activating cellular contraction. Recent measurements of intra-SR (luminal) Ca(2+) suggest a high diffusive Ca(2+)-mobility constant (D(CaSR)). This could help spatially to unify SR Ca(2+)-content ([Ca(2+)](SRT)) and standardize Ca(2+)-release throughout the cell. But measurements of localized depletions of luminal Ca(2+) (Ca(2+)-blinks), associated with local Ca(2+)-release (Ca(2+)-sparks), suggest D(CaSR) may actually be low. Here we describe a novel method for measuring D(CaSR). Using a cytoplasmic Ca(2+)-fluorophore, we estimate regional [Ca(2+)](SRT) from localized, caffeine-induced SR Ca(2+)-release. Caffeine microperfusion of one end of a guinea pig or rat myocyte diffusively empties the whole SR at a rate indicating D(CaSR) is 8-9 microm(2)/s, up to tenfold lower than previous estimates. Ignoring background SR Ca(2+)-leakage in our measurement protocol produces an artifactually high D(CaSR) (>40 microm(2)/s), which may also explain the previous high values. Diffusion-reaction modeling suggests that a low D(CaSR) would be sufficient to support local SR Ca(2+)-signaling within sarcomeres during excitation-contraction coupling. Low D(CaSR) also implies that [Ca(2+)](SRT) may readily become spatially nonuniform, particularly under pathological conditions of spatially nonuniform Ca(2+)-release. Local control of luminal Ca(2+), imposed by low D(CaSR), may complement the well-established local control of SR Ca(2+)-release by Ca(2+)-channel/ryanodine receptor couplons.
authors.affiliation: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy, and Genetics, Oxford University, Oxford OX1 3PT, United Kingdom.
authors.forename: Pawel
authors.initials: P
authors.lastname: Swietach
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: Richard D
authors.initials: RD
authors.lastname: Vaughan-Jones
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism*; D006168:Guinea Pigs; D008954:Models, Biological; D008956:Models, Chemical; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D016276:Ventricular Function
chemical_list: D002118:Calcium