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Multiple Cation Channels Mediate Increases in Intracellular Calcium Induced by the Volatile Irritant, Trans-2-Pentenal in Rat Trigeminal Neurons

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Abstract

Trans-2-Pentenal (pentenal), an α,β-unsaturated aldehyde, induces increases in [Ca2+]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+/Ca2+, as we showed previously, we investigated which types of voltage-gated sodium/calcium channels (VGSCs/VGCCs) are involved in pentenal-induced [Ca2+]i increases as a downstream mechanisms. The application of tetrodotoxin (TTX) significantly suppressed the pentenal-induced increase in [Ca2+]i in a portion of TG neurons, suggesting that TTX-sensitive (TTXs) VGSCs contribute to the pentenal response in those neurons. Diltiazem and ω-agatoxin IVA, antagonists of L- and P/Q-type VGCCs, respectively, both caused significant reductions of the pentenal-induced responses. ω-Conotoxin GVIA, on the other hand, caused only a small decrease in the size of pentenal-induced [Ca2+]i rise. These indicate that both L- and P/Q-type VGCCs are involved in the increase in [Ca2+]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.

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Abbreviations

VOC:

Volatile organic compound

TG:

Trigeminal ganglion

AITC:

Allyl isothiocyanate

VGSC:

Voltage-gated sodium channel

VGCC:

Voltage-gated calcium channel

TTX:

Tetrodotoxin

TRP:

Transient receptor potential

nAChR:

Nicotinic acetylcholine receptor

CGRP:

Calcitonin gene-related peptide

HBSS:

Hank’s balanced salt solution

PS:

Penicillin–streptomycin

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Acknowledgments

Randy Peoples and Valerie Audige provided excellent cell culture support. This research was supported by funding from Japan Tobacco Inc.

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Authors and Affiliations

  1. Tobacco Science Research Center, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, Japan

    Takashi Inoue

  2. Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA, 19104, USA

    Bruce P. Bryant

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  1. Takashi Inoue
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  2. Bruce P. Bryant
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Correspondence to Bruce P. Bryant.

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Inoue, T., Bryant, B.P. Multiple Cation Channels Mediate Increases in Intracellular Calcium Induced by the Volatile Irritant, Trans-2-Pentenal in Rat Trigeminal Neurons. Cell Mol Neurobiol 30, 35–41 (2010). https://doi.org/10.1007/s10571-009-9428-9

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  • DOI: https://doi.org/10.1007/s10571-009-9428-9

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