AI Article Synopsis
- The study focused on measuring local calcium ([Ca](SR)) levels within the sarcoplasmic reticulum (SR) of heart cells to understand how calcium release happens during regular and spontaneous events.
- Researchers used rabbit heart cells to simultaneously measure calcium levels in the cytosol and SR, noting differences in calcium diffusion rates and the presence of calcium gradients.
- Findings highlight that rapid calcium diffusion in the SR may prevent noticeable gradients during regular rhythms, but clear gradients appear during spontaneous calcium sparks, with important implications for heart muscle function and potential arrhythmias.
Article Abstract
Rationale: 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.
Methods And 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084972 | PMC |
| http://dx.doi.org/10.1161/CIRCRESAHA.111.240234 | DOI Listing |
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