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, Ca(2+) directly gates heterologously expressed TRPA1 in whole-cell and excised-patch recordings with an apparent EC(50) 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 Ca(2+)-dependent activation. Furthermore, we determine Ca(2+) as prerequisite for icilin activity on TRPA1.
Doerner
Julia F
JF
Lehrstuhl fuer Zellphysiologie, Fakultaet Biologie, Ruhr-Universitaet Bochum, 44780 Bochum, Germany.
Gisselmann
Günter
G
Hatt
Hanns
H
Wetzel
Christian H
CH
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D007509:Irritants / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011744:Pyrimidinones / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*
D015220:Calcium Channels; D007509:Irritants; D009419:Nerve Tissue Proteins; D011744:Pyrimidinones; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C490483:icilin; D002118:Calcium