Distinct properties of Ca–calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel

Transient receptor potential (TRP) vanilloid 1 (TRPV1) is well recognized as a polymodal molecular pain re­ ceptor that responds to a wide range of stimuli includ­ ing noxious heat >43°C, chemical agonists, and protons (Caterina et al., 1997; Tominaga et al., 1998). TRPV1 responses to these stimuli signal the exposure to ex­ treme temperature or tissue damage to elicit appropri­ ate protective mechanisms. TRPV1 is well characterized for its activation by capsaicin, a naturally occurring compound found in chili peppers (Caterina et al., 1997). Prolonged activation of TRPV1 with capsaicin results in acute desensitization, where TRPV1 activity decreases during the course of stimulation. In contrast, repeated stimulation of TRPV1 results in tachyphy­ laxis, where TRPV1 activation decreases with successive stimulation followed by loss of response to any sub­ sequent stimuli.