Upstream eventTRPV1 activation, TRPV1
Opening of calcium channel, Calcium influx
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Proton donors (e.g. capsacin) cause TRPV1 calcium channels to open, causing localized calcium transients and deplorarization of neuronal membrane which may lead to action potentials.
Evidence Supporting this KER
The basic function of TRPV1 is known and is concordant with existing biological knowledge.
Extensive evidence from in vitro patch clamp and in vivo toxicity studies show that TRPV1 is molecularly sensitive to noxious heat, acids, and proton donors (Caterina et al, 1997, Gavva et al, 2004).
Uncertainties and Inconsistencies
Molecular determinants of TRPV1 agonist activity are not yet fully characterized.
Quantitative Understanding of the Linkage
EC50 values for receptor activation and action potential generation in neurons are known for many TRPV1 agonists. The sensitivity of the response to stimulus may be modified by other cell signals and conditions.