Transient Receptor Potential V1 (TRPV1) is a non selective cation channel with high Ca²⁺ permeability. TRPV1 is subject to polymodal activation via various agents including capsaicin, noxious heat or low extracellular pH. TRPV1 is expressed in peripheral nociceptive neurons. Using endoplasmic reticulum-targeted aequorin, we have directly monitored [Ca²⁺] changes inside the ER ([Ca²⁺]ER) in dorsal root ganglia (DRG) neurons and in HEK293T cells transiently expressing the rat vanilloid receptor. Mobilization of Ca²⁺ from intracellular stores was also assayed by imaging of cytosolic [Ca²⁺] with fura 2-AM. Most of the TRPV1 localized intracellularly and co-localized with ER markers (ER-Tracker or ER-targeted aequorin). Mobilization of Ca²⁺ from ER by capsaicin was studied in the presence of ruthenium red (10 mM) in order to block the capsaicin–induced Ca²⁺ entry from the extracellular medium. Capsaicin emptied the Ca²⁺ stores in a concentration-dependent manner (5-20 mM) both in intact and digitonin-permeabilized cells. Rexiniferatoxin and PPAHV also released Ca²⁺ from the ER.

These results suggest that TRPV1 expressed in the ER is functional, although its affinity for capsaicin maybe smaller than the one achieved by the plasma-membrane-located TRPV1.