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Ca2+ Diffusion and Sarcoplasmic Reticulum Transport Both Contribute to [Ca2+]i Decline During Ca2+ Sparks in Rat Ventricular Myocytes

Abstract : 1. We sought to evaluate the contribution of the sarcoplasmic reticulum (SR) Ca2P pump (vs. diffusion) to the kinetics of [Ca2+], decline during Ca2+ sparks, which are due to spontaneous local SR Ca2+ release, in isolated rat ventricular myocytes measured using fluo-3 and laser scanning confocal microscopy. 2. Resting Ca2+ sparks were compared before (control) and after the SR Ca2+-ATPase was either completely blocked by 5/M thapsigargin (TG) or stimulated by isoprenaline. Nae-Ca2+ exchange was blocked using Na+-free, Ca2+-free solution (0 Na+, 0 Ca2+) and conditions were arranged so that the SR Ca2+ content was the same under all conditions when Ca2+ sparks were measured. 3. The control Ca2P spark amplitude (281 + 13 nM) was not changed by TG (270 + 21 nM) or isoprenaline (302 + 10 nM). However, the time constant of [Ca2+]i decline was significantly slower in the presence of TG (29-3 + 4-3 ms) compared with control (21P6 + 1P5 ms) and faster with isoprenaline (14X5 + 0 9 ms), but in all cases was much faster than the global [Ca2+], decline during a control twitch (177 + 10 ms). 4. The spatial spread of Ca2+ during the Ca2P spark was also influenced by the SR Ca2P pump. The apparent 'space constant' of the Ca2+ sparks was longest when the SR Ca pump was blocked, intermediate in control and shortest with isoprenaline. 5. We conclude that while Ca2P diffusion from the source of Ca2+ release is the dominant process in local [Ca2+]i decline during the Ca2P spark, Ca2P transport by the SR contributes significantly to both the kinetics and spatial distribution of [Ca2+], during the Ca2P spark. Ca2+ sparks are produced when Ca2+ release channels in the sarcoplasmic reticulum (SR) open spontaneously or are triggered to open by a local increase in [Ca2+]i (Cheng,
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Ana Maria Gómez, Heping Cheng, W Lederer, Donald Bers. Ca2+ Diffusion and Sarcoplasmic Reticulum Transport Both Contribute to [Ca2+]i Decline During Ca2+ Sparks in Rat Ventricular Myocytes. The Journal of Physiology, Wiley, 1996, 496, pp.575 - 581. ⟨10.1113/jphysiol.1996.sp021708⟩. ⟨inserm-02477361⟩

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