Direct activation of the ion channel TRPA1 by Ca2+

TRPA1 is an ion channel expressed by nociceptors and activated by irritant compounds such as mustard oil. The endogenous function of TRPA1 has remained unclear, a fact highlighted by ongoing debate over its potential role as a sensor of noxious cold. Here we show that intracellular Ca2+ activates human TRPA1 via an EF-hand domain and that cold sensitivity occurs indirectly ( and nonphysiologically) through increased [Ca2+](i) during cooling in heterologous systems.