Sorting out MIC, TRP, and CRAC Ion Channels

A horde of cation-nonselective ion channel clans populate cell membranes. Their number is further augmented by removing extracellular calcium ([Ca²⁺]_o), turning well-behaved Ca²⁺-selective channels into less discriminating sieves (Kostyuk and Krishtal, 1977; Almers and McCleskey, 1984). The Ca²⁺ ion stems the flood of ions moving through many cation channels by lodging in their throats, obstructing the path for monovalent ions by clinging to acidic groups in the narrow pore (Tsien et al., 1987; Hille, 2001). The trick of reducing [Ca²⁺]_o uncovers channels whose conductances are inconveniently low in physiological solution. One of the most frustratingly low conductance Ca²⁺ channels has been the Ca²⁺ release–activated channel (CRAC) channel (Parekh and Penner, 1997; Lewis, 1999). The CRAC current is typically induced by the “store depletion” protocol...