FIGURE 2.

TRPV1 modulation. Schematic diagram of complex regulation of TRPV1 implicated in pain transduction. TRPV1 channels may not only act as ligand-gated ion channels but may also increase neuron excitability through the activation of intracellular signaling pathways. The activity of TRPV1 is controlled by a multitude of regulatory mechanisms that either causes sensitization or desensitization of the channel. TRPV1 sensitization appears mediated by direct phosphorylation of intracellular protein domains by PKC, PKA, and other kinases. A dynamic balance between phosphorylation and dephosphorylation of TRPV1 by Ca²⁺/calmodulin-dependent kinase II and calcineurin, respectively, appears to control the activation/desensitization state of the channel. TRPV1 activity may be additionally potentiated by Ca²⁺-induced exocytotic recruitment to the cell membrane of an internal pool of vesicular TRPV1.