ABSTRACT
Cells expend energy to maintain a low cytosolic Ca2þ concentration ([Ca2þ]i) relative to extracellular and organelle environments, so periodic fluctuations in cytosolic concentrations can be used to initiate intracellular signaling. Indeed, [Ca2þ]i is 10,000-20,000-fold lower than extracellular [Ca2þ]. Various transmembrane proteins conduct Ca2þ-exhibiting either high (Ca2þ-selective) or low (Ca2þ nonselective) specificity-from outside to inside the cell, in accordance with electrical and chemical ionic gradients. Protein channels open in response to distinct intracellular stimuli. Perhaps most notably, membrane depolarization opens so-called voltage-gated Ca2þ channels. More recently a subset of channels were identified that monitor and respond to endoplasmic reticulum Ca2þ concentrations; when endoplasmic reticulum Ca2þ concentrations decrease, membrane Ca2þ channels open. Transmembrane proteins have now been identified that are specifically activated following endoplasmic reticulum Ca2þ store depletion and thus fulfill the criterion for a ‘‘store-operatedCa2þ entry’’ (SOCE) channel.
