Cinnamaldehyde interacts with the local anesthetic pocket of the NaV 1.5 channel
- 1KU Leuven
Abstract
Cinnamaldehyde (CA) is extensively used as flavorant and in traditional medicine. CA is com-monly used in pain research as specific agonist of TRPA1, a polymodal cation channel expressed in nociceptive primary sensory neurons. However, we previously showed that CA inhibits the L-type Ca2+ channel in cardiac and smooth muscle cells, raising the possibility that other ion channels can be modulated by this compound as well. Here, we investigated whether CA exhibits affects the activity on the cardiac NaV1.5 channel. We used the whole-cell patch-clamp technique to record Na+ currents in HEK293T cells expressing the human NaV1.5 channel, as well as in cells expressing hNaV1.5 channels baring mutation in the binding pocket of local anesthetics (LA). Our results show that CA exhibit LA-like actions on hNaV1.5 channels: CA blocks hNaV1.5 currents in a tonic and voltage-dependent fashion. Residues F1760 and Y1767 are important for the blockade of NaV1.5 by CA and a double point mutation F1760A/Y1767A abolishes the blockade of INa by CA. We conclude that CA and LID share common structural determinants for the inhibition of Na+ channels and that CA has LA-like actions.
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BibTeX
@misc{alvarezcollazo2026cinnamaldehyde,
title = {{Cinnamaldehyde interacts with the local anesthetic pocket of the NaV 1.5 channel}},
author = {J. Alvarez-Collazo and A. Lopez-Requena and A. Talavera and J. L. Alvarez and K. Talavera},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.13.751249},
url = {https://www.biorxiv.org/content/10.64898/2026.09.13.751249v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cinnamaldehyde interacts with the local anesthetic pocket of the NaV 1.5 channel
AU - J. Alvarez-Collazo
AU - A. Lopez-Requena
AU - A. Talavera
AU - J. L. Alvarez
AU - K. Talavera
PY - 2026
DA - 2026/09/13
PB - bioRxiv
DO - 10.64898/2026.09.13.751249
UR - https://www.biorxiv.org/content/10.64898/2026.09.13.751249v1
AB - Cinnamaldehyde (CA) is extensively used as flavorant and in traditional medicine. CA is com-monly used in pain research as specific agonist of TRPA1, a polymodal cation channel expressed in nociceptive primary sensory neurons. However, we previously showed that CA inhibits the L-type Ca2+ channel in cardiac and smooth muscle cells, raising the possibility that other ion channels can be modulated by this compound as well. Here, we investigated whether CA exhibits affects the activity on the cardiac NaV1.5 channel. We used the whole-cell patch-clamp technique to record Na+ currents in HEK293T cells expressing the human NaV1.5 channel, as well as in cells expressing hNaV1.5 channels baring mutation in the binding pocket of local anesthetics (LA). Our results show that CA exhibit LA-like actions on hNaV1.5 channels: CA blocks hNaV1.5 currents in a tonic and voltage-dependent fashion. Residues F1760 and Y1767 are important for the blockade of NaV1.5 by CA and a double point mutation F1760A/Y1767A abolishes the blockade of INa by CA. We conclude that CA and LID share common structural determinants for the inhibition of Na+ channels and that CA has LA-like actions.
ER -