Figure 2.

Schematic diagram depicting Ca²⁺-dependent modulation of TRPV1 desensitization. Influxed Ca²⁺ binds to CaM. Ca²⁺-loaded CaM then binds to the ARD in the N-terminus of TRPV1, displacing the binding of ATP, leading to channel inhibition. Ca²⁺/CaM also binds to the CaM-binding domain (CBD) in the distal C-terminus and activates PP2B anchored on AKAP79/150 that binds to the proximal C-terminus of TRPV1. Activated PP2B removes and antagonizes phosphorylation of TRPV1 (S801) by PKC and PKA that are also anchored on AKAP79/150. Meanwhile, Ca²⁺ induces hydrolysis of PIP₂, further promoting channel desensitization.