Allyl isothiocyanate (AITC) activates nonselective cation currents in human cardiac fibroblasts: possible involvement of TRPA1

The effects of allyl isothiocyanate (AITC), transient receptor potential ankyrin 1 (TRPA1) agonist, on cultured human cardiac fibroblasts were examined by measuring intracellular Ca(2+) concentration [Ca(2+)](i) and whole-cell voltage clamp techniques. AITC (200 μM) increased Ca(2+) entry in the presence of [Ca(2+)](i). Ruthenium red (RR) (30 μM), and La(3+) (0.5 mM), a general cation channel blocker, inhibited AITC-induced Ca(2+) entry. Under the patch pipette filled with Cs(+)- and EGTA-solution, AITC induced the current of a reversal potential (Er) of approximately +0 mV. When extracellular Na(+) ion was changed by NMDG(+), the inward current activated by AITC was markedly reduced. La(3+) and RR inhibited the AITC-induced current. The conventional RT-PCR analysis, Western blot, and immunocytochemical studies showed TRPA1 mRNA and protein expression. The present study shows the first evidence for functional Ca(2+)-permeable nonselective cation currents induced by AITC, possibly via TRPA1 in human cardiac fibroblast.