Ca$^2+$ blinks: rapid nanoscopic store calcium signaling.
Proc. Natl. Acad. Sci. U. S. A., 102 (8):
3099--3104 (February 2005)DOI: 10.1073/pnas.0500059102
Abstract
Luminal Ca$^2+$ in the endoplasmic and sarcoplasmic reticulum
(ER/SR) plays an important role in regulating vital biological processes,
including store-operated capacitative Ca$^2+$ entry, Ca$^2+$-induced
Ca$^2+$ release, and ER/SR stress-mediated cell death. We report
rapid and substantial decreases in luminal Ca$^2+$, called
"Ca$^2+$ blinks," within nanometer-sized stores (the junctional
cisternae of the SR) during elementary Ca$^2+$ release events
in heart cells. Blinks mirror small local increases in cytoplasmic
Ca$^2+$,orCa$^2+$ sparks, but changes of Ca$^2+$ in
the connected free SR network were below detection. Store microanatomy
suggests that diffusional strictures may account for this paradox.
Surprisingly, the nadir of the store depletion trails the peak of
the spark by about 10 ms, and the refilling of local store occurs
with a rate constant of 35 s(-1), which is approximately 6-fold faster
than the recovery of local Ca$^2+$ release after a spark. These
data suggest that both local store depletion and some time-dependent
inhibitory mechanism contribute to spark termination and refractoriness.
Visualization of local store Ca$^2+$ signaling thus broadens
our understanding of cardiac store Ca$^2+$ regulation and function
and opens the possibility for local regulation of diverse store-dependent
functions.
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