Upstream eventTRPA1 activation, TRPA1 Receptor
Opening of calcium channel, Calcium influx
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation||adjacent||High||High|
Life Stage Applicability
Key Event Relationship Description
Electrophiles (e.g. isocyanates, aldehydes) react covalently with ankyrin domains while select non-reactive irritants activate through an uncharacterized alternative mechanism. Both cause localized calcium transients and deplorarization of neuronal membrane which may lead to action potentials.
Evidence Supporting this KER
The basic function of TRPA1 is known and is concordant with existing biological knowledge.
Extensive evidence from in vitro patch clamp and in vivo toxicity studies show that TRPA1 is molecularly sensitive to electrophiles, noxious cold, and other irritants (Jordt et al, 2004, Hinman et al, 2006, Macpherson et al, 2007, Richards et al, 2010).
Uncertainties and Inconsistencies
Some modes of TRPA1 activation are unclear.
Quantitative Understanding of the Linkage
Threshold concentrations (EC50 values) for channel activation and action potential generation are known in the case of many TRPA1 agonists. TRPV1 sensitivity may also be regulated by various other signaling events.