Calcium Signaling Out of the Gate

In one of the cell's key controls of internal calcium levels, channels at the cell membrane open in response to changes in calcium levels in the endoplasmic reticulum (ER). These plasma membrane channels, called calcium-release activated calcium (CRAC) channels, were first identified electrophysiologically about 20 years ago. Because their tiny conductance (about 100 times lower than that of any other known calcium channel) makes individual channel currents very difficult to detect, however, both the molecular mechanism of this signaling pathway and the identity of the channel, have until recently remained a mystery.