Transient receptor potential channel a1 is directly gated by calcium ions

Members of the superfamily of transient receptor potential (TRP) channels are proposed to play important roles in sensory physiology. As an excitatory ion channel TRPA1 is robustly activated by pungent irritants in mustard and garlic and is suggested to mediate the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate that, in addition to pungent natural compounds, Ca2+ directly gates heterologously expressed TRPA1 in whole-cell and excised-patch recordings with an apparent EC50 of 905 nM. Pharmacological experiments and site-directed mutagenesis indicate that the N-terminal EF-hand calcium-binding domain of the channel is involved in Ca2+-dependent activation. Furthermore, we determine Ca2+ as prerequisite for icilin activity on TRPA1.