Figure 3.

TRPV1 is a polymodal cation channel. TRPV1 can be activated by a variety of noxious stimuli such as heat, pH and pressure, and its interaction with other receptors including G protein-coupled receptors (GPCRs) contributes to its polymodal nature. GPCR activation can directly lead to recruitment of PKC and PKA, through phospholipase C and adenylyl cyclase respectively, to phosphorylate TRPV1 and sensitize the channel. Elevations in intracellular calcium from TRPV1 and GPCR stimulation can activate calcineurin and CaMKII via calmodulin to further modulate TRPV1 activity. GPCR: G-protein coupled receptors, AC: adenylyl cyclase, cAMP: cyclic AMP, CaN: calcineurin, DAG: diacylglycerol, PIP2: phosphoinositide 4,5-bisphosphate, IP3: inositol 1,4,5-trisphosphate, PLC: phospholipase C, ER: endoplasmic reticulum.