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Many molecular biological interventions in current use, as well as inheritable disease conditions, modify the intracellular endowment of molecules that bind Ca(2+) or channels and pumps that transfer it to and from intracellular storage organelles. A simple law, named the "cell boundary theorem," states that intracellular alterations cannot directly result in changes in the cytosolic concentration, [Ca(2+)](i), in a true resting state. A demonstration of the validity of this theorem is provided. Several examples are then discussed of interventions or diseases that increase leak of Ca(2+) from storage organelles and result in greater resting [Ca(2+)](i). According to the theorem, the increase in [Ca(2+)](i) cannot be a direct consequence of the greater leak. Its primary cause must be a change of the fluxes at the level of the plasmalemma, caused in turn by the increase in leak through some sort of "store-operated Ca(2+) entry." While the law is discussed in terms of Ca(2+) homeostasis, it applies to any solute that may be transported by the plasma membrane.

The cell boundary theorem: a simple law of the control of cytosolic calcium concentration