ABSTRACT
Because of its pivotal role in regulating many cellular processes, intracellular ‘free’ Ca2+ concentrations are kept at a very low level. This is accomplished by a number of mechanisms.
The bulk of the body’s calcium (99 percent) is stored in the skeleton. However, calcium ions are also dissolved in body fluids, and these extracellular concentrations are high (approximately 1 mM). In sharp contrast, intracellular concentrations of calcium are about four orders of magnitude lower and kept in the range of 100 nM. This enormous concentration gradient constantly causes Ca2+ to leak from extracellular compartments into the cytosol. However, the intracellular concentrations of Ca2+ are rigorously maintained at low levels by both calcium-binding proteins and calcium pumps, i.e. ATP-dependent transporters present in both the plasma membrane and the membranes of the endoplasmic reticulum. These pumps effectively transport Ca2+ either out of the cell or into the ER lumen. Indeed, the ER has compartmentalized Ca2+
at high concentrations (>100 µM), i.e. approximately 1,000-fold higher than in the cytosol.
