Multiple cation channels mediate increases in intracellular calcium induced by the volatile irritant, trans-2-pentenal in rat trigeminal neurons.

Trans-2-Pentenal (pentenal), an alpha,beta-unsaturated aldehyde, induces increases in [Ca(2+)](i) in cultured neonatal rat trigeminal ganglion (TG) neurons. Since all pentenal-sensitive neurons responded to a specific TRPA1 agonist, allyl isothiocyanate (AITC) and neurons from TRPA1 knockouts failed to respond to pentenal, TRPA1 appears to be sole initial transduction site for pentenal-evoked trigeminal response, as reported for the structurally related irritant, acrolein. Furthermore, because the neuronal sensitivity to pentenal is strictly dependent upon the presence of extracellular Na(+)/Ca(2+), as we showed previously, we investigated which types of voltage-gated sodium/calcium channels (VGSCs/VGCCs) are involved in pentenal-induced [Ca(2+)](i) increases as a downstream mechanisms. The application of tetrodotoxin (TTX) significantly suppressed the pentenal-induced increase in [Ca(2+)](i) in a portion of TG neurons, suggesting that TTX-sensitive (TTXs) VGSCs contribute to the pentenal response in those neurons. Diltiazem and omega-agatoxin IVA, antagonists of L- and P/Q-type VGCCs, respectively, both caused significant reductions of the pentenal-induced responses. omega-Conotoxin GVIA, on the other hand, caused only a small decrease in the size of pentenal-induced [Ca(2+)](i) rise. These indicate that both L- and P/Q-type VGCCs are involved in the increase in [Ca(2+)](i) produced by pentenal, while N-type calcium channels play only a minor role. This study demonstrates that TTXs VGSCs, L- and P/Q-type VGCCs play a significant role in the pentenal-induced trigeminal neuronal responses as downstream mechanisms following TRPA1 activation.