Abstract
Wherever you travel through the cytoplasm of the cells you will find
organelles with internal Ca$^2+$ levels higher than in the
surrounding cytosol. This is particularly true of the endoplasmic
reticulum (ER) (or sarcoplasmic reticulum (SR) in muscle cells);
such organelles serve as the main sources of releasable Ca$^2+$
for cytosolic cellular signalling. Calcium pumps of the SERCA family
(sarcoplasmic and endoplasmic reticulum calcium ATP-ases) import
calcium into the organelle lumen. The other mechanism that is responsible
for the steady state calcium level within the lumen of ER or SR is
a calcium leak that balances the influx created by the pumps. The
leak remains the most enigmatic of the processes involved in calcium
regulation. The molecular nature of the leak mechanism is not known.
The basal leak is a relatively slow process, which is difficult to
investigate and which is easily outmatched (both in the amplitude
of calcium responses and in attractiveness to experimenters) by substantially
faster second messenger-induced release. Nevertheless, information
on the properties of the calcium leak, although thinly scattered
through the pages of PubMed, has been slowly accumulating. In this
review we will discuss the properties of the calcium leak and speculate
about possible mechanisms, which could mediate this process.
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