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Cell Calcium. 2017 Dec;68:34-44. doi: 10.1016/j.ceca.2017.10.003. Epub 2017 Oct 18.

Differential cytotoxicity and intracellular calcium-signalling following activation of the calcium-permeable ion channels TRPV1 and TRPA1.

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Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University Faculty of Medicine, Israel; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel.
Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany. Electronic address:


Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons. While activation of TRPV1 by the vanilloids capsaicin, resiniferatoxin and anandamide results in calcium-dependent cell death, activation by protons and the oxidant chloramine-T failed to reduce cell viability. The TRPA1-agonists acrolein, carvacrol and capsazepine all induced cytotoxicity, but this effect is independent of TRPA1. Activation of both TRPA1 and TRPV1 triggers a strong influx of external calcium, but also a strong calcium-release from intracellular stores most likely including the endoplasmic reticulum (ER). Activation of TRPV1, but not TRPA1 also results in a strong increase of mitochondrial calcium both in HEK 293 cells and mouse DRG neurons. Our data demonstrate that activation of TRPV1, but not TRPA1 mediates a calcium-dependent cell death. While both receptors mediate a release of calcium from intracellular stores, only activation of TRPV1 seems to mediate a robust and probably lethal increase in mitochondrial calcium.


Cell death; Endoplasmic reticulum; Intracellular calcium; Mitochondria; Sensory neurons; TRP channel

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