In skeletal muscle cells, Ca²⁺ ions are concentrated and stored in the sarcoplasmic reticulum (SR), a specialized type of endoplasmic reticulum (ER). The release (via ion channels) of stored Ca²⁺ ions from the SR lumen into the cytosol causes muscle contraction, as discussed in Chapter 17. A P-class Ca²⁺ ATPase located in the SR membrane pumps Ca²⁺ from the cytosol back into the lumen of the SR, thereby inducing muscle relaxation.

In the cytosol of muscle cells, the free Ca²⁺ concentration ranges from 10⁻⁷ M (resting cells) to more than 10⁻⁶ M (contracting cells), whereas the total Ca²⁺ concentration in the SR lumen can be as high as 10⁻² M. The lumen of the SR contains two abundant proteins, calsequestrin and the so-called high-affinity Ca²⁺ binding protein, each of which binds multiple Ca²⁺ ions at high affinity. By binding much of the Ca²⁺ in the SR lumen, these proteins reduce the concentration of “free” Ca²⁺ ions in the SR vesicles. This reduction, in turn, reduces the Ca²⁺ concentration gradient between the cytosol and the SR lumen and consequently reduces the energy needed to pump Ca²⁺ ions into the SR from the cytosol. The activity of the muscle Ca²⁺ ATPase increases as the free Ca²⁺ concentration in the cytosol rises. In skeletal muscle cells, the calcium pump in the SR membrane works in concert with a similar Ca²⁺ pump located in the plasma membrane to ensure that the cytosolic concentration of free Ca²⁺ in resting muscle remains below 0.1 µM.