The Basal Thermal Sensitivity of the TRPV1 Ion Channel Is Determined by PKCβII

Peripheral nociceptors are excited by the activation of membrane receptors and ion channels. The heat-sensitive TRPV1 ion channel responds to various noxious chemical and thermal stimuli, causing pain and itch. Here, we show that TRPV1 is coexpressed with PKC beta II in a subset of mouse sensory neurons and that, in these neurons, TRPV1 binds directly to PKC beta II, leading to the activation and translocation of PKC beta II. Activated PKC beta II, in turn, significantly increases the responsiveness of TRPV1 by phosphorylating Thr705. The heat sensitivity of TRPV1 is almost eliminated by either knocking down PKC beta II or mutating Thr705; however, neither of these manipulations affects the potentiation of TRPV1 caused by the activation of PKC epsilon. PKC beta II thus acts as an auxiliary subunit of TRPV1 by forming a population-dependent TRPV1 ion channel complex controlling the sensitivity of TRPV1 and setting the threshold for pain and itch.